  Reference population databases are an essential tool in variant and gene
interpretation. Their use guides the identification of pathogenic variants
amidst the sea of benign variation present in every human genome, and supports
the discovery of new disease-gene relationships. The Genome Aggregation
Database (gnomAD) is currently the largest and most widely used publicly
available collection of population variation from harmonized sequencing data.
The data is available through the online gnomAD browser
(https://gnomad.broadinstitute.org/) that enables rapid and intuitive variant
analysis. This review provides guidance on the content of the gnomAD browser,
and its usage for variant and gene interpretation. We introduce key features
including allele frequency, per-base expression levels, constraint scores, and
variant co-occurrence, alongside guidance on how to use these in analysis, with
a focus on the interpretation of candidate variants and novel genes in rare
disease.
