In Silico Functional Annotation and Variant Effect Prediction of BRCA1 Mutation (rs80357389)

The BRCA1 (Breast Cancer 1) tumor suppressor gene is critical for maintaining genomic stability via Homologous Recombination Repair. Pathogenic germline mutations in BRCA1 lead to Hereditary Breast and Ovarian Cancer syndromes. With Next-Generation Sequencing, massive genomic variant data is generated daily, making it challenging to differentiate benign polymorphisms from functional, disease-causing variants. This study presents an integrated computational pipeline to perform functional annotation and variant effect evaluation of the single nucleotide polymorphism rs80357389 in the BRCA1 locus. We designed an automated, reproducible workflow using Python for genetic variant parsing. Evolutionary conservation constraint scores from SIFT and PolyPhen-2 were evaluated via REST APIs. High-resolution chromosomal coordinate mapping and transcript annotation were executed using open cloud bioinformatics structures. The objective is to provide a script-based tool for rapid, accurate assessment of BRCA1 variants to aid in clinical interpretation.