NM_007294.3(BRCA1):c.5468-10_5468-9del AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Jul 23, 2021)

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_007294.3(BRCA1):c.5468-10_5468-9del]


BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
Cytogenetic location:
Genomic location:
Preferred name:
  • NC_000017.11:g.43045812_43045813GA[1]
  • NG_005905.2:g.172170_172171CT[1]
  • NM_007294.3:c.5468-10_5468-9del
  • NM_007297.4:c.5327-10_5327-9del
  • NM_007298.3:c.2156-10_2156-9del
  • NM_007299.4:c.2082-10_2082-9del
  • NM_007300.4:c.5531-10_5531-9del
  • LRG_292t1:c.5468-10_5468-9del
  • LRG_292:g.172170_172171CT[1]
  • NC_000017.10:g.41197828_41197829del
  • NC_000017.10:g.41197829_41197830GA[1]
  • NM_007294.3:c.5468-10_5468-9delCT
  • U14680.1:n.5587-10_5587-9delCT
Nucleotide change:
Breast Cancer Information Core (BIC) (BRCA1): 5587-10&base_change=del CT; dbSNP: rs273902770
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_007294.3:c.5468-10_5468-9del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007297.4:c.5327-10_5327-9del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007298.3:c.2156-10_2156-9del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.2082-10_2082-9del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007300.4:c.5531-10_5531-9del - intron variant - [Sequence Ontology: SO:0001627]


MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000566231GeneDxcriteria provided, single submitter
Likely benign
(Sep 7, 2017)
germlineclinical testing

Citation Link,

SCV000699258Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Jul 23, 2021)
germlineclinical testing

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

Citation Link

Summary from all submissions

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



BRCA1 and BRCA2 genetic testing in Hispanic patients: mutation prevalence and evaluation of the BRCAPRO risk assessment model.

Vogel KJ, Atchley DP, Erlichman J, Broglio KR, Ready KJ, Valero V, Amos CI, Hortobagyi GN, Lu KH, Arun B.

J Clin Oncol. 2007 Oct 10;25(29):4635-41.

PubMed [citation]

Details of each submission

From GeneDx, SCV000566231.4

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


This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699258.4

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


Variant summary: BRCA1 c.5468-10_5468-9delCT alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8.8e-05 in 250484 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast And Ovarian Cancer Syndrome (8.8e-05 vs 0.001), allowing no conclusion about variant significance. The variant, c.5468-10_5468-9delCT, has been reported in the literature in one individual affected with breast cancer (Vogel_2007). The report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as benign (n=2) and likely benign (n=2). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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

Last Updated: Aug 7, 2021

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