Fig. 8: Flowchart summarizing the study design.

Using sequencing data of 96,691 female breast cancer cases and 302,116 unaffected controls from the Breast Cancer Association Consortium (BCAC), the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium and the UK Biobank (UKB) we calculated case-control likelihood ratios (LRs) and odds ratios (ORs) for 11,207 BRCA1 and BRCA2 variants, of which 6909 are coding (coding sequence, CDS ± 5 bp). Derived LRs and ORs were further aligned to ACMG/AMP evidence strengths to provide evidence in favor of or against pathogenicity following sensitivity analyses-derived variant exclusion criteria.