rs763162379

Description

This variant is denoted BRIP1 c.3096T>G at the cDNA level, p.Ser1032Arg (S1032R) at the proteinlevel, and results in the change of a Serine to an Arginine (AGT>AGG). This variant has not, to our knowledge, beenpublished in the literature as pathogenic or benign. BRIP1 Ser1032Arg was not observed at a significant allelefrequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek2016). Since Serine and Arginine differ in some properties, this is considered a semi-conservative amino acidsubstitution. BRIP1 Ser1032Arg occurs at a position that is not conserved and is located within the BRCA1 bindingdomain (Cantor 2011). In silico analyses predict that this variant is unlikely to alter protein structure or function. Basedon currently available evidence, it is unclear whether BRIP1 Ser1032Arg is a pathogenic or benign variant. Weconsider it to be a variant of uncertain significance.

The p.S1032R variant (also known as c.3096T>G), located in coding exon 19 of the BRIP1 gene, results from a T to G substitution at nucleotide position 3096. The serine at codon 1032 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. 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.