17-61776394-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The ENST00000259008.7(BRIP1):c.2097+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,613,980 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000259008.7 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.2097+7G>A | splice_region_variant, intron_variant | ENST00000259008.7 | NP_114432.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.2097+7G>A | splice_region_variant, intron_variant | 1 | NM_032043.3 | ENSP00000259008 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00235 AC: 357AN: 152166Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00225 AC: 566AN: 251276Hom.: 2 AF XY: 0.00214 AC XY: 290AN XY: 135812
GnomAD4 exome AF: 0.00298 AC: 4360AN: 1461696Hom.: 13 Cov.: 30 AF XY: 0.00284 AC XY: 2064AN XY: 727150
GnomAD4 genome AF: 0.00234 AC: 357AN: 152284Hom.: 1 Cov.: 32 AF XY: 0.00205 AC XY: 153AN XY: 74462
ClinVar
Submissions by phenotype
not provided Benign:8
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2024 | BRIP1: BP4, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jun 30, 2022 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
not specified Benign:5
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 16, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 22, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 22, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Hereditary cancer-predisposing syndrome Benign:4
Likely benign, no assertion criteria provided | clinical testing | True Health Diagnostics | Jun 18, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. | May 23, 2018 | - - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Oct 19, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 18, 2015 | - - |
Familial cancer of breast Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Mar 01, 2023 | This variant is considered benign. Homozygosity for this variant has been confirmed in one or more individuals lacking clinical features consistent with gene-specific recessive disease, indicating that this variant is unlikely to be pathogenic. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Sep 19, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Fanconi anemia complementation group J Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Jun 03, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Breast and/or ovarian cancer Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Apr 25, 2023 | - - |
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Malignant tumor of breast Benign:1
Benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The BRIP1 c.2097+7G>A variant was identified in 3 of 436 proband chromosomes (frequency: 0.007) from individuals or families with breast or ovarian cancer and was identified in 1 of 146 control chromosomes (frequency: 0.005) from healthy individuals (Guenard_2008, Rutter_2003, Vahteristo_2006). The variant was also identified in dbSNP (ID: rs4988352) “With Uncertain significance allele”, ClinVar (classified benign by Invitae, GeneDx, likely benign by Counsyl, Quest Diagnostics Nichols Institute San Juan Capistrano and Color Genomics Inc, and uncertain significance by Illumina), Clinvitae (6x), Zhejiang Colon Cancer Database (7x), and was not identified in Cosmic or MutDB. The variant was identified in control databases in 644 of 277018 chromosomes (2 homozygous) at a frequency of 0.002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: African in 8 of 24028 chromosomes (freq: 0.0003), Other in 10 of 6462 chromosomes (freq: 0.002), Latino in 72 of 34396 chromosomes (freq: 0.002), European Non-Finnish in 518 (1 homozygous) of 126558 chromosomes (freq: 0.004), European Finnish in 34 (1 homozygous) of 25788 chromosomes (freq: 0.001), and South Asian in 2 of 30780 chromosomes (freq: 0.00007); it was not observed in the Ashkenazi Jewish and East Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. - |
Ovarian neoplasm Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Jun 03, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at