17-61849151-C-T
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_032043.3(BRIP1):c.485G>A(p.Arg162Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,613,430 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R162L) has been classified as Uncertain significance.
Frequency
Consequence
NM_032043.3 missense
Scores
Clinical Significance
Conservation
Publications
- familial ovarian cancerInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- Fanconi anemiaInheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina
- Fanconi anemia complementation group JInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- hereditary breast carcinomaInheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- colorectal adenomaInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
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ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152010Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000119 AC: 3AN: 251330 AF XY: 0.0000221 show subpopulations
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461302Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727004 show subpopulations
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74368 show subpopulations
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
This missense variant replaces arginine with glutamine at codon 162 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 been detected in a breast cancer case-control meta-analysis in 1/60466 cases and 1/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRIP1_000689) and an unaffected individual and absent in suspected hereditary breast and ovarian cancer families (PMID: 29368626). This variant also has been reported in individuals affected with head and neck carcinoma and metastatic osteosarcoma (PMID: 28678401, 29507082). This variant has been identified in 3/251330 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. -
The p.R162Q variant (also known as c.485G>A), located in coding exon 4 of the BRIP1 gene, results from a G to A substitution at nucleotide position 485. The arginine at codon 162 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. -
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Uncertain:1Benign:1
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not provided Uncertain:1
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27978560, 29507082, 28678401, 29368626, 31822803, 11301010) -
Familial cancer of breast Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at