rs777213170

Description

This variant is denoted BRIP1 c.3209C>A at the cDNA level and p.Ser1070Ter (S1070X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TAA). Although this variant has not, to our knowledge, been published in the literature as a germline variant, it has been reported as a confirmed somatic variant in ovarian cancer (Beltrame 2015). BRIP1 Ser1070Ter results in the loss of 180 amino acids at the end of the protein, the clinical significance of which is unclear, as the lost region is not within any known functional domain. Due to the location of the newly created nonsense codon in the last exon, the transcript is not expected to undergo nonsense-mediated decay and could therefore encode a truncated protein that retains some normal function. BRIP1 Ser1070Ter was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Based on currently available evidence, it is unclear whether BRIP1 Ser1070Ter is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.