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NM_007294.4(BRCA1):c.5407-4C>G

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(4);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
7 (Most recent: Sep 23, 2021)
Last evaluated:
Jul 27, 2020
Accession:
VCV000233348.10
Variation ID:
233348
Description:
single nucleotide variant
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NM_007294.4(BRCA1):c.5407-4C>G

Allele ID
235928
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q21.31
Genomic location
17: 43047707 (GRCh38) GRCh38 UCSC
17: 41199724 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.41199724G>C
LRG_292:g.170277C>G
LRG_292t1:c.5407-4C>G
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000017.11:43047706:G:C
Functional consequence
functionally_normal [Sequence Ontology SO:0002219]
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5407-4C>G, a SPLICE REGION variant, produced a function score of 0.42, 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
-
Links
ClinGen: CA10580483
dbSNP: rs876660347
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 2 criteria provided, multiple submitters, no conflicts Mar 5, 2020 RCV000222294.3
Likely benign 1 criteria provided, single submitter Jul 27, 2020 RCV000343466.5
Uncertain significance 1 criteria provided, single submitter May 7, 2020 RCV000433879.3
Uncertain significance 2 criteria provided, single submitter Jan 12, 2018 RCV001073214.2
Likely benign 1 criteria provided, single submitter Apr 10, 2019 RCV001697223.1
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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
12040 12208

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Jan 12, 2018)
criteria provided, single submitter
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000403053.3
Submitted: (Feb 20, 2020)
Evidence details
Comment:
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 … (more)
Likely benign
(Mar 05, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000277702.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (1)
Comment:
In silico models in agreement (benign);Intact protein function observed in appropriate functional assay(s);RNA Studies
Likely benign
(Jul 27, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Invitae
Accession: SCV000636039.3
Submitted: (Jan 07, 2021)
Evidence details
Likely benign
(Apr 10, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000532626.5
Submitted: (Sep 23, 2021)
Evidence details
Comment:
This variant is associated with the following publications: (PMID: 30209399)
Likely benign
(Feb 24, 2016)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000906438.1
Submitted: (Nov 06, 2018)
Evidence details
Uncertain significance
(May 07, 2020)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001370707.1
Submitted: (Jul 01, 2020)
Evidence details
Comment:
Variant summary: BRCA1 c.5407-4C>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly … (more)
not provided
(-)
no assertion provided
Method: in vitro
Breast-ovarian cancer, familial 1
Allele origin: not applicable
Brotman Baty Institute,University of Washington
Accession: SCV001238731.1
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:0.418894311836247
Brotman Baty Institute,University of Washington
Accession: SCV001238731.1
Submitted: (Nov 12, 2018)
Evidence details
Publications
PubMed (1)
Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5407-4C>G, a SPLICE REGION variant, produced a function score of 0.42, 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
https://sge.gs.washington.edu/BRCA1/ - - - -

Text-mined citations for rs876660347...

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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 Nov 27, 2021