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NM_007294.4(BRCA1):c.5572A>C (p.Ile1858Leu) AND not provided

Germline classification:
Likely benign (1 submission)
Last evaluated:
Mar 24, 2016
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000588511.5

Allele description

NM_007294.4(BRCA1):c.5572A>C (p.Ile1858Leu)

Gene:
BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.4(BRCA1):c.5572A>C (p.Ile1858Leu)
Other names:
5691A>C
HGVS:
  • NC_000017.11:g.43045698T>G
  • NG_005905.2:g.172286A>C
  • NM_007294.4:c.5572A>CMANE SELECT
  • NM_007297.4:c.5431A>C
  • NM_007298.3:c.2260A>C
  • NM_007299.4:c.*86A>C
  • NM_007300.4:c.5635A>C
  • NP_009225.1:p.Ile1858Leu
  • NP_009225.1:p.Ile1858Leu
  • NP_009228.2:p.Ile1811Leu
  • NP_009229.2:p.Ile754Leu
  • NP_009231.2:p.Ile1879Leu
  • LRG_292t1:c.5572A>C
  • LRG_292:g.172286A>C
  • LRG_292p1:p.Ile1858Leu
  • NC_000017.10:g.41197715T>G
  • NM_007294.3:c.5572A>C
  • NR_027676.2:n.5749A>C
  • p.I1858L
Protein change:
I1811L
Links:
BRCA1-HCI: BRCA1_00097; dbSNP: rs765656957
NCBI 1000 Genomes Browser:
rs765656957
Molecular consequence:
  • NM_007299.4:c.*86A>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_007294.4:c.5572A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007297.4:c.5431A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007298.3:c.2260A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007300.4:c.5635A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027676.2:n.5749A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: CN517202

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000699274Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely benign
(Mar 24, 2016) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS).

Lindor NM, Guidugli L, Wang X, Vallée MP, Monteiro AN, Tavtigian S, Goldgar DE, Couch FJ.

Hum Mutat. 2012 Jan;33(1):8-21. doi: 10.1002/humu.21627. Epub 2011 Nov 3. Review.

PubMed [citation]
PMID:
21990134
PMCID:
PMC3242438

A guide for functional analysis of BRCA1 variants of uncertain significance.

Millot GA, Carvalho MA, Caputo SM, Vreeswijk MP, Brown MA, Webb M, Rouleau E, Neuhausen SL, Hansen Tv, Galli A, Brandão RD, Blok MJ, Velkova A, Couch FJ, Monteiro AN; ENIGMA Consortium Functional Assay Working Group..

Hum Mutat. 2012 Nov;33(11):1526-37. doi: 10.1002/humu.22150. Epub 2012 Jul 16. Review.

PubMed [citation]
PMID:
22753008
PMCID:
PMC3470782
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699274.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: The variant c.5572A>C affects a not conserved nucleotide, resulting in amino acid change from Ile to Leu. 4/4 in-silico tools predict this variant to be benign. This variant was found in 8/120940 control chromosomes including the large and broad populations of ExAC at a frequency of 0.0000661. It was only found in South Asian population; its allele frequency in South Asian cohort from ExAC is 0.0004 (7/16392 chromosomes). These frequencies do not exceed the maximal expected frequency of a pathogenic allele (0.0010005); however, it may still suggest that this variant is a rare polymorphism in the South Asians. In a study reported by Juwle et al 2012, this variant's frequency in 100 control chromosomes was 0.01 and the authors call the variant as a polymorphism. Despite the small sample size, selection of the controls is quite appropriate in the study, i.e. they used elderly control subjects. From a genetic analysis (employing co-occurrence in trans of a VUS with known deleterious mutations; detailed analysis, by logistic regression, of personal and family history of cancer in VUS-carrying probands; and, in a subset of probands, an analysis of cosegregation with disease in pedigrees), this variant was found to have high odds in favor of neutrality and a very low probability of being deleterious (Easton_2007, Lindor_2012). One clinical lab as well as reputable databases has classified this variant as benign. Taken together, this variant has currently been classified as Probable Normal Variant or Likely Benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 10, 2022