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NM_007294.4(BRCA1):c.5074+1G>T

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Interpretation:
Pathogenic​

Review status:
reviewed by expert panel
Submissions:
10 (Most recent: Sep 9, 2021)
Last evaluated:
Jun 18, 2019
Accession:
VCV000037630.7
Variation ID:
37630
Description:
single nucleotide variant
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NM_007294.4(BRCA1):c.5074+1G>T

Allele ID
46186
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q21.31
Genomic location
17: 43067607 (GRCh38) GRCh38 UCSC
17: 41219624 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_007294.3:c.5074+1G>T splice donor
LRG_292:g.150377G>T
LRG_292t1:c.5074+1G>T
... more HGVS
Protein change
-
Other names
IVS17+1G>T
Canonical SPDI
NC_000017.11:43067606:C:A
Functional consequence
functionally_abnormal [Sequence Ontology SO:0002218]
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5074+1G>T, a CANONICAL SPLICE variant, produced a function score of -1.45, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute,University of Washington]
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
Breast Cancer Information Core (BIC) (BRCA1): 5193+1&base_change=G to T
ClinGen: CA003194
dbSNP: rs80358053
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 5 reviewed by expert panel Jun 18, 2019 RCV000031211.9
Pathogenic 1 criteria provided, single submitter Aug 2, 2016 RCV000482341.1
Pathogenic 2 criteria provided, single submitter Feb 27, 2020 RCV000496776.2
Pathogenic 1 criteria provided, single submitter Jan 27, 2016 RCV000772123.1
Pathogenic 1 criteria provided, single submitter Dec 1, 2013 RCV001659877.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
BRCA1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
12270 12437

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jun 18, 2019)
reviewed by expert panel
Method: curation
Breast-ovarian cancer, familial 1
Allele origin: germline
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV001161633.1
Submitted: (Jul 23, 2019)
Evidence details
Publications
PubMed (1)
Comment:
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on … (more)
Pathogenic
(Jan 27, 2016)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000905198.1
Submitted: (Nov 06, 2018)
Evidence details
Pathogenic
(Oct 02, 2015)
criteria provided, single submitter
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000326133.3
Submitted: (Oct 28, 2016)
Evidence details
Pathogenic
(Aug 02, 2016)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000568399.4
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted BRCA1 c.5074+1G>T or IVS16+1G>T and consists of a G>T nucleotide substitution at the +1 position of intron 16 of the BRCA1 … (more)
Pathogenic
(Feb 27, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Invitae
Accession: SCV001585897.1
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (8)
Comment:
This sequence change affects a donor splice site in intron 16 of the BRCA1 gene. It is expected to disrupt RNA splicing and likely results … (more)
Pathogenic
(Dec 01, 2013)
criteria provided, single submitter
Method: curation
Breast-ovarian cancer, familial 1
Breast-ovarian cancer, familial 2
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Research and Development, ARUP Laboratories
Accession: SCV001877439.1
Submitted: (Sep 09, 2021)
Evidence details
Publications
PubMed (2)
Other databases
https://arup.utah.edu/database/B…
Pathogenic
(Apr 12, 1999)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145289.1
Submitted: (Mar 28, 2014)
Evidence details
Likely pathogenic
(Mar 20, 2007)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Sharing Clinical Reports Project (SCRP)
Accession: SCV000053811.3
Submitted: (Jul 24, 2012)
Evidence details
Pathogenic
(Jan 31, 2014)
no assertion criteria provided
Method: research
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587451.1
Submitted: (Aug 04, 2017)
Evidence details
not provided
(-)
no assertion provided
Method: in vitro
Breast-ovarian cancer, familial 1
Allele origin: not applicable
Brotman Baty Institute,University of Washington
Accession: SCV001237535.1
Submitted: (Nov 12, 2018)
Evidence details
Publications
PubMed (1)

Functional evidence

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Functional consequence Method Result Submitter Supporting information
functionally_abnormal
  1. saturation genome editing in haploid cells
  2. Method citation(s):
  1. LOSS_OF_FUNCTION:-1.44841651036631
Brotman Baty Institute,University of Washington
Accession: SCV001237535.1
Submitted: (Nov 12, 2018)
Evidence details
Publications
PubMed (1)
Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5074+1G>T, a CANONICAL SPLICE variant, produced a function score of -1.45, corresponding to a functional classification of … (more)

Citations for this variant

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Title Author Journal Year Link
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification. Parsons MT Human mutation 2019 PMID: 31131967
Accurate classification of BRCA1 variants with saturation genome editing. Findlay GM Nature 2018 PMID: 30209399
BRCA germline mutations in an unselected nationwide cohort of Chinese patients with ovarian cancer and healthy controls. Li A Gynecologic oncology 2018 PMID: 30078507
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. Rebbeck TR Human mutation 2018 PMID: 29446198
BRCA1/BRCA2 gene mutations/SNPs and BRCA1 haplotypes in early-onset breast cancer patients of Indian ethnicity. Juwle A Medical oncology (Northwood, London, England) 2012 PMID: 22752604
Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. Borg A Human mutation 2010 PMID: 20104584
Splicing in action: assessing disease causing sequence changes. Baralle D Journal of medical genetics 2005 PMID: 16199547
Characterization of two novel BRCA1 germ-line mutations involving splice donor sites. Brose MS Genetic testing 2004 PMID: 15345110
Incidence of BRCA1 and BRCA2 mutations in young Korean breast cancer patients. Choi DH Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2004 PMID: 15117986
https://arup.utah.edu/database/BRCA/Variants/BRCA1.php - - - -
https://sge.gs.washington.edu/BRCA1/ - - - -

Text-mined citations for rs80358053...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 18, 2021