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NM_007294.4(BRCA1):c.5193+3A>G

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Jan 7, 2021)
Last evaluated:
Feb 18, 2020
Accession:
VCV000409301.9
Variation ID:
409301
Description:
single nucleotide variant
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NM_007294.4(BRCA1):c.5193+3A>G

Allele ID
402037
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q21.31
Genomic location
17: 43063330 (GRCh38) GRCh38 UCSC
17: 41215347 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.41215347T>C
LRG_292:g.154654A>G
LRG_292t1:c.5193+3A>G
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000017.11:43063329:T:C
Functional consequence
functionally_normal [Sequence Ontology SO:0002219]
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5193+3A>G, 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
Trans-Omics for Precision Medicine (TOPMed) 0.00004
Links
ClinGen: CA16615375
dbSNP: rs1060502326
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Feb 18, 2020 RCV000474996.6
Uncertain significance 1 criteria provided, single submitter Nov 16, 2018 RCV000781031.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Jun 29, 2018 RCV000562931.2
not provided 1 no assertion provided - RCV001076962.1
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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
12038 12206

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Jan 01, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000910205.1
Submitted: (Nov 06, 2018)
Evidence details
Uncertain significance
(Nov 16, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000918796.1
Submitted: (Apr 24, 2019)
Evidence details
Comment:
Variant summary: BRCA1 c.5193+3A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly … (more)
Uncertain significance
(Jun 29, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000661034.3
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The c.5193+3A>G intronic variant results from an A to G substitution 3 nucleotides after coding exon 17 in the BRCA1 gene. This nucleotide position is … (more)
Uncertain significance
(Feb 18, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Invitae
Accession: SCV000549266.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change falls in intron 18 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein, … (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: SCV001242815.1
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:0.00191534061506178
Brotman Baty Institute,University of Washington
Accession: SCV001242815.1
Submitted: (Nov 12, 2018)
Evidence details
Publications
PubMed (1)
Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5193+3A>G, 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
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. Buratti E Nucleic acids research 2007 PMID: 17576681
Statistical features of human exons and their flanking regions. Zhang MQ Human molecular genetics 1998 PMID: 9536098
https://sge.gs.washington.edu/BRCA1/ - - - -

Text-mined citations for rs1060502326...

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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 10, 2021