rs575998972

Description

Variant summary: BRIP1 c.3188C>T (p.Ser1063Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 246196 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3188C>T in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

Curator: Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa.

The p.S1063L variant (also known as c.3188C>T), located in coding exon 19 of the BRIP1 gene, results from a C to T substitution at nucleotide position 3188. The serine at codon 1063 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well conserved on limited sequence alignment. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.