Overview
Today we announce the latest update to our tool, the Genetic Prevalence and Incidence Estimator (GenIE, https://genie.broadinstitute.org), which now includes estimates of genetic incidence of de novo variation (GIDNV). This new feature uses gnomAD v4.1.1 constraint data to estimate the frequency of suspected de novo disease-causing variation at zygote creation.

Today, we released gnomAD v4.1.1, which includes an update to our gene constraint metrics, LOFTEE flags, and a minor update to other flags and annotations. In this blog post, we discuss the improvements incorporated in this release, our new LOEUF threshold recommendations, and guidance around interpretation of the gene constraint metrics.

We updated our gene constraint metrics following the release of gnomAD v4.0. gnomAD v4.0 expanded the scale of our constraint calculations…

Today we are pleased to announce the incorporation of cumulative counts of gnomAD individuals carrying pairs of rare co-occurring variants within genes in the gnomAD v2 browser, across various allele frequencies and functional consequences. These counts can be used to evaluate how frequently rare variant co-occurrence is observed in a large reference population. We envision that this data will aid the medical genetics community in interpreting the clinical significance of rare co-occurring variants found in patients, in the context of autosomal recessive disease. This feature builds off of our variant co-occurrence (inferred phasing) work (see “Variant Co-Occurrence (Phasing) Information in gnomAD”).