More than two million humans have now had their exomes or genomes sequenced, but the underlying data are typically heavily siloed by project and generated using inconsistent sequencing and analysis technologies. Harmonizing these data represents a tremendous opportunity to understand the distribution of genetic variants across human genes, and their impact on human phenotypes and disease risk. In this talk I will describe work done as part of the Genome Aggregation Database (gnomAD) project and

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... its predecessor, the Exome Aggregation Consortium (ExAC), to harmonize exome and genome sequencing data from over 130,000 individuals. I will describe the construction of this resource, and the ways it can be used to interpret individual genetic variants, to identify genes (and regions of genes) depleted of functional variation, and to characterize human 'knockouts' across a range of populations.