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NM_007294.4(BRCA1):c.4657T>A (p.Leu1553Met)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: Jan 7, 2021)
Last evaluated:
Feb 29, 2020
Accession:
VCV000055254.5
Variation ID:
55254
Description:
single nucleotide variant
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NM_007294.4(BRCA1):c.4657T>A (p.Leu1553Met)

Allele ID
69921
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q21.31
Genomic location
17: 43074349 (GRCh38) GRCh38 UCSC
17: 41226366 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.41226366A>T
NC_000017.11:g.43074349A>T
NM_007294.4:c.4657T>A MANE Select NP_009225.1:p.Leu1553Met missense
... more HGVS
Protein change
L1553M, L1506M, L449M, L1574M
Other names
p.L1553M:TTG>ATG
4776T>A
Canonical SPDI
NC_000017.11:43074348:A:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA002952
dbSNP: rs80357431
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 3 criteria provided, single submitter Jul 24, 2017 RCV000112375.1
Uncertain significance 1 criteria provided, single submitter Jan 17, 2020 RCV000164710.4
Uncertain significance 1 criteria provided, single submitter Jul 10, 2015 RCV000212184.1
Uncertain significance 1 criteria provided, single submitter Feb 29, 2020 RCV001364498.1
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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
11983 12150

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Jul 24, 2017)
criteria provided, single submitter
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: unknown
Counsyl
Accession: SCV000785404.2
Submitted: (Jun 20, 2018)
Evidence details
Uncertain significance
(Jul 10, 2015)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000210183.13
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted BRCA1 c.4657T>A at the cDNA level, p.Leu1553Met (L1553M) at the protein level, and results in the change of a Leucine to … (more)
Uncertain significance
(Jan 17, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000215379.5
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The p.L1553M variant (also known as c.4657T>A), located in coding exon 13 of the BRCA1 gene, results from a T to A substitution at nucleotide … (more)
Uncertain significance
(Feb 29, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Invitae
Accession: SCV001560651.1
Submitted: (Jan 07, 2021)
Evidence details
Comment:
This sequence change replaces leucine with methionine at codon 1553 of the BRCA1 protein (p.Leu1553Met). The leucine residue is moderately conserved and there is a … (more)
Uncertain significance
(Dec 23, 2003)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145142.1
Submitted: (Mar 28, 2014)
Evidence details
Uncertain significance
(May 08, 2009)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Sharing Clinical Reports Project (SCRP)
Accession: SCV000297614.1
Submitted: (Dec 29, 2015)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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There are no citations in ClinVar for this variation. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs80357431...

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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 Apr 18, 2021