ExAC

ExAC, short for Exome Aggregation Consortium, is a public resource that aggregates human exome sequencing data to provide high-resolution estimates of genetic variant frequencies. The dataset combines exome sequencing data from dozens of studies, totaling tens of thousands of individuals, with the aim of enabling researchers and clinicians to interpret genetic variation more accurately. Samples are de-identified and curated to include unrelated individuals and standardized variant calls, with representation across multiple ancestral populations including European, Finnish, African, Latino, East Asian, and South Asian groups.

ExAC provides allele frequencies, counts, and quality metrics for observed variants, with per-population frequencies as well as overall frequencies. It also introduced gene-level constraint metrics, notably the probability of loss-of-function intolerance (pLI), which estimates how tolerant a gene is to protein-truncating variants and aids in prioritizing candidate disease genes. The resource is widely used to filter out variants that are too common in the general population to plausibly cause rare Mendelian disorders and to inform the interpretation of both research and clinical sequencing results.

History and legacy: ExAC was developed by the Exome Aggregation Consortium and released publicly in the mid-2010s. In subsequent years, ExAC data were incorporated into the Genome Aggregation Database (gnomAD), which expanded the dataset to include whole-genome data in addition to exomes. As a result, ExAC is no longer updated as a standalone resource, but its data underpins contemporary gnomAD releases and related population-genetics analyses. See also gnomAD and variant interpretation.