New gnomAD v4 Constraint Metrics (hg38) and gnomAD Non-cancer filter (hg19/hg38)

[Gerardo Perez]

Hello Everyone,

We are pleased to announce the release of the gnomAD v4 constraint metrics for human assembly hg38/GRCh38 and the addition of a non-cancer filter for the GRCh37/hg19 Exome Variants v2.1.1 and the hg38/GRCh38 Genome Variants v3.1.1 tracks.

The gnomAD v4 constraint metrics tracks contain metrics of pathogenicity per-gene as predicted for gnomAD v4.0 and identifies genes subject to strong selection against various classes of mutation. These tracks contain metrics of pathogenicity per-gene as predicted for gnomAD v4.0 and identifies genes subject to strong selection against various classes of mutation. The release of the gnomAD v4 constraint metrics consists of two new subtracks in the gnomAD Constraint Metrics composite track:

1. Transcript LoF Constraint track: Predicted constraint metrics at the whole transcript level for three different types of variation: missense, synonymous, and predicted loss of function.
2. Transcript Missense Constraint track: The missense constraint tracks are built similarly to the LoF constraint tracks, however the items displayed are based on missense Z scores. All items are colored black, and individual Z scores can be seen on mouseover.

The GRCh37/hg19 Exome Variants v2.1.1 and the hg38/GRCh38 Genome Variants v3.1.1 tracks now have a non-cancer filter that allows the option to exclude/include variants from samples of individuals who were not ascertained for having cancer in a cancer study. These non-cancer subsets follow the new guidelines for clinical variant testing of BRCA1 and BRCA2 genes and are used for the assessment of breast cancer patients.

We would like to thank the Genome Aggregation Database Consortium for making these data available. We would also like to thank Chris Lee, Ana Benet-Pagès, Gerardo Perez, and Jairo Navarro for the creation and release of these tracks.