Description
Variant Summary: The c.671-8A>G variant involves the alteration of a non-conserved nucleotide resulting in an intronic change. This variant is located at a position that is not widely known to affect splicing, 3/5 splicing prediction programs via Alamut predict no significant effect on splicing, and mutation taster predicts the variant to be a polymorphism. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.012%, predominantly observed in the East Asian subpopulation at a frequency of 0.18%. This frequency exceeds the maximal expected allele frequency for a pathogenic variant in BRCA1 (0.10%), suggesting this is a benign polymorphism found primarily in population(s) of East Asian origin. The variant has been reported in multiple databases to co-occur in individuals with pathogenic BRCA1 variants including two patients with c.2296_2297delAG, p.Ser766X (UMD), one patient with c.68_69delAG, p.Glu23ValfsX17 (UMD), and one patient with c.188T>A, p.Leu63Ter (BIC). Taken together, the multiple co-occurrences with pathogenic variants along with the intronic nature of the variant and the relatively high frequency in the East Asian population, this variant was classified as Benign.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
