ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.3693A>G (p.Ile1231Met)

gnomAD frequency: 0.00001  dbSNP: rs1046992728
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569978 SCV000668926 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-10 criteria provided, single submitter clinical testing The p.I1231M variant (also known as c.3693A>G), located in coding exon 19 of the BRIP1 gene, results from an A to G substitution at nucleotide position 3693. The isoleucine at codon 1231 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is not well 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.
Mendelics RCV000989970 SCV001140732 likely benign Familial cancer of breast 2024-04-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001055410 SCV001219798 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2024-12-04 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1231 of the BRIP1 protein (p.Ile1231Met). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596, 35534704). ClinVar contains an entry for this variant (Variation ID: 483173). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRIP1 protein function with a negative predictive value of 95%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000989970 SCV003807202 uncertain significance Familial cancer of breast 2022-08-12 criteria provided, single submitter clinical testing ACMG classification criteria: PM2 moderated, BP4 supporting

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