17-61849151-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 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
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.485G>A | p.Arg162Gln | missense_variant | 5/20 | ENST00000259008.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.485G>A | p.Arg162Gln | missense_variant | 5/20 | 1 | NM_032043.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152010Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251330Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135828
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461302Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727004
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 09, 2023 | 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 alteration has been identified in one individual from a North American cohort of individuals diagnosed with early onset colon cancer (Pearlman R et al. JAMA Oncol. 2017 Apr;3:464-471) and in one patient from a study consisting of 417 individuals with head and neck squamous cell carcinoma diagnosed before age 50 undergoing genetic testing of 16 Fanconi anemia genes (Chandrasekharappa SC et al. Cancer 2017 Oct;123:3943-3954). This variant was not present in a large cohort of 6341 breast cancer patients and 706 ovarian cancer patients, but was identified in 2/36687 controls (Weber-Lassalle N et al. Breast Cancer Res. 2018 Jan;20:7). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Sep 19, 2023 | 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. - |
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 21, 2023 | 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
Uncertain significance, no assertion criteria provided | clinical testing | Zotz-Klimas Genetics Lab, MVZ Zotz Klimas | Oct 30, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at