Projects gnomAD

Exome Aggregation Consortium (ExAC) launched at the Broad Institute with exome data from 61,486 individuals across multiple disease-specific and population genetic studies. Provided the first comprehensive reference of population genetic variation, transforming variant interpretation in medical genetics.

ExAC v1.0 published in Nature (Lek et al., 2016), analyzing exome data from 60,706 individuals. This landmark resource cataloged over 10 million variants, established allele frequency filters for clinical variant interpretation, and demonstrated that most genes are extremely tolerant of loss-of-function variation. The ExAC browser became the de facto standard for variant annotation.

Rebranded to Genome Aggregation Database (gnomAD) with broadened scope. gnomAD v2.1 released 125,748 exomes and 15,708 genomes — a massive expansion over ExAC. Introduced population-specific allele frequency data across multiple ancestral groups and provided the most comprehensive catalog of human genetic variation to date.

gnomAD v3 released 71,702 whole genomes aligned to GRCh38, providing coverage of both coding and non-coding regions. Enabled genome-wide constraint metrics and non-coding variant interpretation. The transition to GRCh38 improved compatibility with modern genomic analyses.

gnomAD v2.1.1 updated the exome dataset with improved QC and additional samples. v3.1 updated the genome dataset with new call sets and expanded to include structural variant (SV) calls. Introduced comprehensive SV resource across 14,891 genomes, revealing thousands of previously uncharacterized structural variants.

gnomAD v4 dramatically expanded to 807,098 exomes and 76,215 genomes, with substantially improved ancestral diversity. v4 included >30 genetic ancestry groups, enabling more precise population-specific allele frequency estimates. New constraint metrics across diverse ancestries and improved structural variant calls made this the most comprehensive human variation resource ever created.