rs117820198
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_032043.3(BRIP1):c.918+15T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000881 in 1,602,738 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0012 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00085 ( 17 hom. )
Consequence
BRIP1
NM_032043.3 intron
NM_032043.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.37
Genes affected
BRIP1 (HGNC:20473): (BRCA1 interacting helicase 1) The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant 17-61808452-A-T is Benign according to our data. Variant chr17-61808452-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 136583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-61808452-A-T is described in Lovd as [Benign]. Variant chr17-61808452-A-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00119 (181/152296) while in subpopulation EAS AF= 0.0327 (170/5192). AF 95% confidence interval is 0.0287. There are 5 homozygotes in gnomad4. There are 100 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 5 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.918+15T>A | intron_variant | ENST00000259008.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.918+15T>A | intron_variant | 1 | NM_032043.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00118 AC: 179AN: 152178Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.00306 AC: 767AN: 250380Hom.: 11 AF XY: 0.00284 AC XY: 384AN XY: 135366
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GnomAD4 exome AF: 0.000849 AC: 1231AN: 1450442Hom.: 17 Cov.: 30 AF XY: 0.000832 AC XY: 601AN XY: 722178
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GnomAD4 genome ? AF: 0.00119 AC: 181AN: 152296Hom.: 5 Cov.: 32 AF XY: 0.00134 AC XY: 100AN XY: 74478
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:15
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 05, 2014 | 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. - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Fanconi anemia complementation group J Benign:2
Benign, criteria provided, single submitter | clinical testing | Counsyl | Jul 05, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 03, 2021 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, no assertion criteria provided | clinical testing | University of Washington Department of Laboratory Medicine, University of Washington | Dec 01, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 08, 2015 | - - |
Breast and/or ovarian cancer Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jul 05, 2021 | - - |
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | 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 r.(spl?) variant was identified in 9 of 714 proband chromosomes (frequency: 0.01) from individuals or families with breast cancer and was not identified in 1728 control chromosomes from healthy individuals (Cao 2009). The variant was also identified in dbSBP (ID: rs117820198) as other, ClinVar and Clinvitae (benign by Counsyl, Color Genomics, GeneDx; and likely benign by Illumina and University of Washington), Zhejiang Colon Cancer Database (1x as unknown) databases. The variant was not identified in Cosmic or MutDB databases. The variant was also identified by our laboratory in 1 individuals with breast cancer who is of Asian descent. The variant was identified in control databases in 777 of 276108 chromosomes (11 homozygous individuals) at a frequency of 0.003 increasing the likelihood that this may be a low frequency benign variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations at a frequency greater than 1%: East Asian in 751 of 18858 chromosomes (freq: 0.04). 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. - |
Familial cancer of breast Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Ovarian neoplasm Benign:1
Benign, criteria provided, single submitter | clinical testing | Counsyl | Jul 05, 2016 | - - |
Hereditary breast ovarian cancer syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | National Health Laboratory Service, Universitas Academic Hospital and University of the Free State | Apr 19, 2022 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at