NM_007294.3(BRCA1):c.3756_3759delGTCT (p.Ser1253Argfs) AND not provided

Clinical significance:Pathogenic (Last evaluated: Jun 15, 2017)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:

Allele description

NM_007294.3(BRCA1):c.3756_3759delGTCT (p.Ser1253Argfs)

BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
Cytogenetic location:
Genomic location:
Preferred name:
NM_007294.3(BRCA1):c.3756_3759delGTCT (p.Ser1253Argfs)
Other names:
3874del4; 3875_3878delGTCT
  • NC_000017.11:g.43091772_43091775delAGAC
  • NG_005905.2:g.126209_126212delGTCT
  • NM_007294.3:c.3756_3759delGTCT
  • NM_007298.3:c.788-743_788-740delGTCT
  • NP_009225.1:p.Ser1253Argfs
  • LRG_292t1:c.3756_3759del
  • LRG_292:g.126209_126212del
  • LRG_292p1:p.Ser1253Argfs
  • NC_000017.10:g.41243789_41243792delAGAC
  • NM_007294.3:c.3756_3759del
  • NR_027676.1:n.3892_3895delGTCT
  • U14680.1:c.3756_3759delGTCT
  • U14680.1:n.3875_3878delGTCT
  • p.S1253Rfs*10
  • p.S1253RfsX10
  • p.Ser1253Argfs*10
Nucleotide change:
Breast Cancer Information Core (BIC) (BRCA1): 3874&base_change=del TGTC; Breast Cancer Information Core (BIC) (BRCA1): 3875&base_change=del GTCT; OMIM: 113705.0014; dbSNP: rs80357868
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_007294.3:c.3756_3759delGTCT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_007298.3:c.788-743_788-740delGTCT - intron variant - [Sequence Ontology: SO:0001627]
  • NR_027676.1:n.3892_3895delGTCT - non-coding transcript variant - [Sequence Ontology: SO:0001619]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000210046GeneDxcriteria provided, single submitter
(Jun 15, 2017)
germlineclinical testing

Citation Link,

SCV000296325Quest Diagnostics Nichols Institute San Juan Capistranocriteria provided, single submitter
(Apr 15, 2015)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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



A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

Development and Validation of a Next-Generation Sequencing Assay for BRCA1 and BRCA2 Variants for the Clinical Laboratory.

Strom CM, Rivera S, Elzinga C, Angeloni T, Rosenthal SH, Goos-Root D, Siaw M, Platt J, Braastadt C, Cheng L, Ross D, Sun W.

PLoS One. 2015;10(8):e0136419. doi: 10.1371/journal.pone.0136419.

PubMed [citation]

Details of each submission

From GeneDx, SCV000210046.11

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


This deletion of four nucleotides in BRCA1 is denoted c.3756_3759delGTCT at the cDNA level and p.Ser1253ArgfsX10 (S1253RfsX10) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GTCT[delGTCT]AAGA. The deletion causes a frameshift, which changes a Serine to an Arginine at codon 1253, and creates a premature stop codon at position 10 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.3756_3759delGTCT, also denoted 3875del4 using alternate nomenclature, has been published in association with breast and ovarian cancers (Castilla 1994, Zhang 2011, Alsop 2012, Gaj 2012, Ghiorzo 2012, George 2013). This variant is also a well-described pathogenic founder variant in the French-Canadian population in Quebec (Janavicius 2010). We consider this variant to be pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000296325.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 30, 2019

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