The 302,355 UKB exome sequences were processed at AstraZeneca from their unaligned FASTQ state. A custom-built Amazon Web Services (AWS) cloud compute platform running Illumina DRAGEN Bio-IT Platform Germline Pipeline v3.0.7 was used to align the reads to the GRCh38 genome reference and perform single-nucleotide variant (SNV) and insertion and deletion (indel) calling. SNVs and indels were annotated using SnpEFF v4.348 against Ensembl Build 38.9249. We further annotated all variants with their genome Aggregation Database (gnomAD) MAFs (gnomAD v2.1.1 mapped to GRCh38)27. We also annotated missense variants with MTR and REVEL scores35,50.
