Submissions for variant NM_032043.3(BRIP1):c.97C>T (p.Leu33Phe)

gnomAD frequency: 0.00001  dbSNP: rs772319724

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000562728	SCV000661569	uncertain significance	Hereditary cancer-predisposing syndrome	2023-08-15	criteria provided, single submitter	clinical testing	The p.L33F variant (also known as c.97C>T), located in coding exon 2 of the BRIP1 gene, results from a C to T substitution at nucleotide position 97. The leucine at codon 33 is replaced by phenylalanine, an amino acid with highly similar 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001054310	SCV001218619	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2023-07-10	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 33 of the BRIP1 protein (p.Leu33Phe). This variant is present in population databases (rs772319724, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 479456). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRIP1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health	RCV000562728	SCV004360308	uncertain significance	Hereditary cancer-predisposing syndrome	2022-04-05	criteria provided, single submitter	clinical testing	This missense variant replaces leucine with phenylalanine at codon 33 of the BRIP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/282716 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.