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NM_007294.3(BRCA1):c.5467+8G>A

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(2);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
8 (Most recent: Jan 7, 2021)
Last evaluated:
Nov 17, 2020
Accession:
VCV000091651.9
Variation ID:
91651
Description:
single nucleotide variant
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NM_007294.3(BRCA1):c.5467+8G>A

Allele ID
97128
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q21.31
Genomic location
17: 43047635 (GRCh38) GRCh38 UCSC
17: 41199652 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.41199652C>T
NC_000017.11:g.43047635C>T
NM_007298.3:c.2155+8G>A
... more HGVS
Protein change
-
Other names
IVS23+8G>A
Canonical SPDI
NC_000017.11:43047634:C:T
Functional consequence
functionally_normal [Sequence Ontology SO:0002219]
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5467+8G>A, a SPLICE REGION variant, produced a function score of 0, corresponding to a functional classification of FUNCTIONAL. 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
The Genome Aggregation Database (gnomAD) 0.00029
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00001
Links
Breast Cancer Information Core (BIC) (BRCA1): 5586+8&base_change=G to A
ClinGen: CA003615
dbSNP: rs80358062
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 3 criteria provided, multiple submitters, no conflicts Aug 16, 2019 RCV000588816.5
Likely benign 1 criteria provided, single submitter Sep 26, 2016 RCV000776226.1
Likely benign 1 criteria provided, single submitter Nov 17, 2020 RCV001089242.2
Conflicting interpretations of pathogenicity 3 no assertion criteria provided Apr 10, 2013 RCV000077168.6
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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
Uncertain significance
(Oct 31, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699257.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (2)
Comment:
Variant summary: The BRCA1 c.5467+8G>A variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts a benign outcome for this substitution along with … (more)
Likely benign
(Nov 17, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Invitae
Accession: SCV000636042.5
Submitted: (Jan 07, 2021)
Evidence details
Uncertain significance
(Nov 29, 2013)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000210223.10
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted BRCA1 IVS22+8G>A or c.5467+8G>A and consists of a G>A nucleotide substitution at the +8 position of intron 22 of the BRCA1 … (more)
Likely benign
(Sep 26, 2016)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000911426.1
Submitted: (Nov 06, 2018)
Evidence details
Uncertain significance
(Aug 16, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600422.2
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (2)
Benign
(Apr 10, 2013)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Sharing Clinical Reports Project (SCRP)
Accession: SCV000108965.4
Submitted: (Dec 30, 2013)
Evidence details
Uncertain significance
(May 29, 2002)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145524.1
Submitted: (Mar 28, 2014)
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: SCV001243381.1
Submitted: (Nov 12, 2018)
Evidence details
Publications
PubMed (1)

Functional evidence

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Functional consequence Method Result Submitter Supporting information
functionally_normal
  1. saturation genome editing in haploid cells
  2. Method citation(s):
  1. FUNCTIONAL:-0.00111794307643816
Brotman Baty Institute,University of Washington
Accession: SCV001243381.1
Submitted: (Nov 12, 2018)
Evidence details
Publications
PubMed (1)
Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5467+8G>A, a SPLICE REGION variant, produced a function score of 0, corresponding to a functional classification of … (more)

Citations for this variant

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Title Author Journal Year Link
Accurate classification of BRCA1 variants with saturation genome editing. Findlay GM Nature 2018 PMID: 30209399
Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer. Wong-Brown MW Breast cancer research and treatment 2015 PMID: 25682074
Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. Judkins T Cancer research 2005 PMID: 16267036
https://sge.gs.washington.edu/BRCA1/ - - - -

Text-mined citations for rs80358062...

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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 Jun 14, 2021