Exome sequencing identifies a recurrent variant in SERPINA3 associating with hereditary susceptibility to breast cancer

•Breast cancer has a strong inherited component that causes familial clustering.•Using exome sequencing we establish SERPINA3 as a novel predisposing gene.•This provides further tools for the clinical breast cancer risk assessment.•SERPINA3 encodes as a plasma protease inhibitor frequently aberrated in cancer.•Function of SERPINA3 proposes new mechanisms for breast cancer pathogenesis.