NM_007294.4(BRCA1):c.3724A>G (p.Thr1242Ala) AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Mar 5, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_007294.4(BRCA1):c.3724A>G (p.Thr1242Ala)]

NM_007294.4(BRCA1):c.3724A>G (p.Thr1242Ala)

BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_007294.4(BRCA1):c.3724A>G (p.Thr1242Ala)
Other names:
  • NC_000017.11:g.43091807T>C
  • NG_005905.2:g.126177A>G
  • NM_007294.3:c.3724A>G
  • NM_007294.4:c.3724A>GMANE SELECT
  • NM_007297.4:c.3583A>G
  • NM_007298.3:c.788-775A>G
  • NM_007299.4:c.788-775A>G
  • NM_007300.4:c.3724A>G
  • NP_009225.1:p.Thr1242Ala
  • NP_009225.1:p.Thr1242Ala
  • NP_009228.2:p.Thr1195Ala
  • NP_009231.2:p.Thr1242Ala
  • LRG_292t1:c.3724A>G
  • LRG_292:g.126177A>G
  • LRG_292p1:p.Thr1242Ala
  • NC_000017.10:g.41243824T>C
  • NR_027676.2:n.3901A>G
  • U14680.1:n.3843A>G
  • p.T1242A
Protein change:
dbSNP: rs80357037
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_007298.3:c.788-775A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.788-775A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007294.3:c.3724A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007294.4:c.3724A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007297.4:c.3583A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007300.4:c.3724A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027676.2:n.3901A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]


Hereditary cancer-predisposing syndrome
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000184855Ambry Geneticscriteria provided, single submitter
Uncertain significance
(Mar 5, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV000909585Color Health, Inccriteria provided, single submitter
Likely benign
(Jul 14, 2016)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing



Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia.

Wen WX, Allen J, Lai KN, Mariapun S, Hasan SN, Ng PS, Lee DS, Lee SY, Yoon SY, Lim J, Lau SY, Decker B, Pooley K, Dorling L, Luccarini C, Baynes C, Conroy DM, Harrington P, Simard J, Yip CH, Mohd Taib NA, Ho WK, et al.

J Med Genet. 2018 Feb;55(2):97-103. doi: 10.1136/jmedgenet-2017-104947. Epub 2017 Oct 9.

PubMed [citation]

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

Details of each submission

From Ambry Genetics, SCV000184855.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)


The p.T1242A variant (also known as c.3724A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 3724. The threonine at codon 1242 is replaced by alanine, an amino acid with similar properties. This alteration has been detected in 1/2575 unselected patients with breast cancer and 0/2809 healthy control individuals from a Malaysian cohort (Wen WX et al. J. Med. Genet. 2018 02;55:97-103). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV000909585.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 20, 2021

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