Updated transcript tissue expression and proportion expressed across transcripts (pext) tracks have been added to the gene pages in the gnomAD v4 browser.

The Hail Tables that underlie the gnomAD browser are now available for public use. These tables closely mirror the structure of the browser, enabling users familiar with the gene and variant pages to easily access the full set of underlying data in a format consistent with the browser’s organization.

For more information about these tables, please refer to our help text on the browser release tables.

To download these tables, visit our downloads page.

This changelog entry discusses smaller updates to gnomAD added with the v4.1 release that were not discussed in the blog post.

The CSV file containing the information in the variant table for a given gene has been corrected to display the proper counts for each genetic ancestry group.

Any user utilizing a CSV file generated from a v4 gene page should re-download the CSV file to ensure they have the correct data.

The exome chromsome Y VCF that was originally released on November 1st, 2023 was a duplicate of the genome chromosome Y VCF. The duplicate has been replaced by the correct VCF as November 16th, 2023.

The regional missense constraint (RMC) track has now been added to the gene pages in the gnomAD v2 browser.

The ClinVar variants track now includes an option to filter by review status. ClinVar assigns a review status to each variant, along with a corresponding number of gold stars, ranging from 0 to 4 stars.

Users will now be able to filter ClinVar variants based on review status by selecting one of the following options from a dropdown: 0-4 Stars, >=1 Stars, >=2 Stars, >=3 Stars, 4 Stars.

Previously, performing a search in the Variant table would remove all neighboring rows from view, leaving only the exact search results displayed. This often resulted in a loss of context regarding a variant’s position in the table and its surrounding variants.

Now, there is an option to enable the display of nearby variants. When “Display neighboring variants” is selected, users are able to search for specific variants and also view nearby variants in the table. As users search, the table automatically jumps to the first search result, which is highlighted.

Previously, for a given population, when a variant had an allele number (AN) of 0, the Allele Frequency (AF) in the population frequencies table would be displayed as 0. This was misleading, as it implied understanding of the frequency of the variant, where there was none.

Now, in those cases, the AF is now displayed as a ’-’ character. This helps users distinguish at a glance when there is no frequency information known about a variant for a given population or subpopulation.

The ClinVar track on Gene pages had several bugs that were identified and fixed, resulting in a more stable and accurate experience for users.

Previously, when selecting a gnomAD variant dataset in the search bar or in the dataset selection dropdown, the dataset’s reference genome version was not displayed.

With this change, the reference genome version (GRCh37 or GRCh38) is now visible next to the gnomAD variant dataset version, making it more clear to users which dataset to select.

The ordering of the links on the navigation bar has been updated to reflect the frequency of their usage. The order of the links is now: About, Team, Policies, Publications, Blog, Changelog, Downloads, Help/FAQ.

In addition, the link formerly titled “News” is now “Blog”, and the link formerly titled “Help” is now titled “Help/FAQ”.

The link to the variant interpretation paper on the home page has been updated to a more recent publication.

Previously, the variant co-occurrence table on the gene page incorrectly rendered on v3 datasets. This was unintentional and misleading, as the analysis was not performed on v3.

Now, the co-occurrence table only renders on v2 datasets, as intended.

The contact page (previously the feedback page) has had its contents updated for clarity.

A link to the All of Us (AoU) data browser has been added to the variant pages under the “External resources” section. This lets users quickly navigate to the same variant on the AoU data browser.

Previously, when a user searched for a gene, a gene that had an alternate symbol that closely matched the search term could appear first in the list of suggested gene symbols. This led to confusing behavior and the need to pay close attention to which results the search bar returned.

Now, any gene with a canonical symbol that matches the search term is prioritized in the list of search results. This results in an overall more intuitive user experience when searching for genes by symbol.

As an example, the search term ABCD previously would result in the gene CX3CL1 as the first search result, as ABCD-3 is an alternate symbol for CX3CL1. With this change, searching for ABCD now results in ABCD1 as the first search result, as it prioritizes canonical gene symbols.

The gnomAD browser’s backend database has had a major version update applied. It is now running Elasticsearch 7 and was previously running Elasticsearch 6. This update has been tested thoroughly and should represent no change in functionality or service.

The team page has been updated to reflect changes in gnomAD staff and council.

The gnomAD browser’s public GraphQL API has had its language updated to TypeScript, from JavaScript. This update has been tested thoroughly and should represent no change in functionality or service.

The publications page has been updated to include a more up to date list of publications, as well as to update the citation format to denote which authors contributed equally.

With the update of the publications page, the citations topic on the help page has been removed. The citations topic URL now redirects to the updated publications page.

Previously, users that wanted to go to the corresponding gene page, from a variant page, would scroll down to the “Variant Effect Predictor” section of the variant page, and click on one of the gene links. In cases where many distinct variant pages were open, users expressed interest in a more direct way to go to the gene page.

With this change, a button labeled “Gene” has been added to the header row of a variant page where there is a single canonical transcript. This button allows users to quickly navigate to the gene that the variant falls in. In the rare case where there is no single canonical transcript, there is no gene page button, and users should instead use the Variant Effect Predictor section.

In order to accomodate the extra button, the phrase Single Nucleotide Variant has been abbreviated to SNV on the corresponding variant pages.

A favicon has been added to the gnomAD browser. This will help users to distinguish which tabs are gnomAD at a glance. The favicon is styled like the coverage plot, showing coverage for both exomes and genomes.

The gnomAD Downloads Page has been redesigned to make it easier to explore datasets released by the gnomAD production team and gnomAD-affiliated research groups.

Previously, if a variant had an Other Splice loss of function flag as a consequence, the variant table would incorrectly display both a Low Confidence flag (LC pLoF), as well as the Other Splice flag (OS pLoF).

Now, in those cases, table only displays the Other Splice flag.

The team page has been updated to include headshots and bios for gnomAD staff members.

The variant table displayed on Gene, Region, and Transcript pages now includes a possible ‘Monoallelic’ flag. This flag labels sites where all samples have homozygous alternate genotypes.

A new team page centralizes information about the people who work on the gnomAD project. Pertinent information that was previously located on the About page has been moved to Teams, and additional details about the team have been added.

The policies page, previously titled ‘terms’, has been updated to cover additional policies. New policies include, but are not limited to, data privacy, ethics, and open science.

The gene and transcript pages show variants located in or within 75 bases of a coding exon. For genes and transcripts with large coding regions, this can result in data in the tracks being difficult to see when it is condensed into a small area on the screen. Now, you can zoom in on genes and transcripts to focus on data in a specific region.

The browser has been updated to show data from gnomAD v3.1.2. For more information about changes in this version, see the gnomAD v3.1.2 blog post.

For variants where a ClinGen Canonical Allele ID is available, a link to the ClinGen Allele Registry has been added to the “External Resources” section on the variant page.

The mean depth of coverage at a variant’s locus can now be found on the variant page after the variant’s allele frequency information.

For genes with a MANE Select transcript, the MANE Select transcript is displayed on the gene page. The browser now displays data from MANE release 0.95.

Previously, viewing structural variants in the browser required looking up a gene or region in gnomAD v2 and then switching to the structural variant dataset.

Now, structural variants can be directly navigated to by selecting “gnomAD SVs v2.1” in the search box on the home page.

Responses to our user survey confirmed that population frequencies are one of the most popular and widely used features of gnomAD. Reflecting that, the population frequencies table has been moved to the top of the variant page to make it more easily accessible.

Detailed information about ClinVar variants, such as submissions, is now available in the ClinVar variants track on gene, region, and transcript pages.

To help identify biologically relevant transcripts, the gene page includes information from the GTEx project on transcripts’ expression in different tissues.

Transcript tissue expression information from the GTEx project has been added to the individual tissue pext tracks.

Today, we are pleased to announce the incorporation of variant co-occurrence (inferred phasing) information in the gnomAD v2 browser. Phase refers to the genetic relationship between a pair of variants; that is, whether the variants are on the same copy of the gene (cis) or on different copies of the gene (trans). We are releasing inferred phasing data for all pairs of variants within a gene where both variants have a global allele frequency in gnomAD exomes <5% and are either coding, flanking intronic (from position -1 to -3 in acceptor sites, and +1 to +8 in donor sites) or in the 5’/3’ UTRs. This encompasses 20,921,100 pairs of variants across 19,685 genes. We envision that this data will be of tremendous help to the medical genetics community in identifying and interpreting co-occurring variants in the context of recessive conditions.

See more information in the full blog post.

We recently removed all gnomAD VCFs from our public buckets, as these files are now hosted via public dataset programs on three major cloud…

• We corrected:

  1. dbSNP rsIDs. The dbSNP resource we used to annotate rsIDs was not split for multi-allelic variants, so if a variant was…

Last year, as part of an effort to reduce costs, we shifted our public Hail-formatted tables into requester-pays buckets. In keeping with our commitment to make gnomAD data as free and accessible to the world as possible, we continued to make VCFs free to download, paying for these downloads ourselves.

Over the last year, we’ve worked with major cloud providers to make these VCFs available for free via their public dataset programs. We’ve decided, as a result, to remove gnomAD VCF files from our own bucket, and encourage users to make use of the (identical) VCF files hosted by our cloud partners.

On variant pages you can now quickly switch between genome builds and gnomAD versions using our new liftover feature. This is available on v2 and v3 variants.

gnomAD v3.1.1 contains some minor corrections and changes to the v3.1 data release. The major annotations, including allele count, allele number, and allele frequency, as well as variant filtering status, remain unchanged for the entire callset and for all subsets of the callset (except the change noted below about switching to Null instead of 0).

A new help page brings together content that was previously divided between different areas of the browser. Now all content, including frequently asked questions and help popups, can be searched in one place.

The ClinVar track can now be filtered by VEP consequence category (pLoF, missense / inframe indel, synonymous, other) as well as pathogenicity.

In the population frequencies table for gnomAD v2.1.1 and gnomAD structural variants, we have changed the labels we use to classify individuals by chromosomal sex from “male” and “female” to “XY” and “XX,” respectively. More detail on the reason for this change can be found in the gnomAD v3.1 blog post.

Transcript pages now note if the transcript is the MANE Select or Ensembl canonical transcript for its gene.

Population frequencies are now available for mitochondrial variants.

The variant table now supports selecting which columns to show and changing the order of columns.

The ClinVar track can now be filtered to only show ClinVar variants that also appear in gnomAD.