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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., Version 3: Includes updates to mirror the latest features and layouts available on the gnomAD browser and general improvements to text and figures (clarifications, typos, additional references etc.) as well as the addition of Table S1, S2, Figure S1, S2 and S5

Additional file 13. Review history.

Additional file 1: Supplementary Material. Supplementary Tables, Figures and Information.

Supplementary methods. Detailed methods description regarding classification of COPD, sequencing protocol and linkage disequilibrium analysis. (DOCX 123 kb)

Targeted genes and variants for targeted high throughput sequencing. The table lists the selected genes and variants included in the study. (DOCX 79 kb)

Probe sets replicated in both replication sets (UBC and Groningen) in the lung eQTL analyses. A table of replicated probe sets in the lung eQTL analysis. (DOCX 38 kb)

Pairwise linkage disequilibrium (LD) of associated variants. A list of detected genetic variants found to be in LD. (DOCX 46 kb)

A plot containing genomic positions and p-values of variants in the CHRNA3/CHRNA5 gene locus with rs8040869 and rs16969968 highlighted. (PDF 144 kb)

Gene burden analysis of common variants. The table present the SKAT analysis of gene burden of common variants. (DOCX 86 kb)

Number of rare variants found uniquely in cases and controls. The table present data of the UNIQ test of rare variants in cases versus controls. (DOCX 78 kb)