U.S. flag

An official website of the United States government

NM_032043.3(BRIP1):c.1140+3del AND Hereditary cancer-predisposing syndrome

Germline classification:
Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:
Jun 16, 2021
Review status:
criteria provided, conflicting classifications
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:
RCV001525783.6

Allele description [Variation Report for NM_032043.3(BRIP1):c.1140+3del]

NM_032043.3(BRIP1):c.1140+3del

Gene:
BRIP1:BRCA1 interacting DNA helicase 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
17q23.2
Genomic location:
Preferred name:
NM_032043.3(BRIP1):c.1140+3del
HGVS:
  • NC_000017.11:g.61801250del
  • NG_007409.2:g.67310del
  • NM_032043.3:c.1140+3delMANE SELECT
  • LRG_300t1:c.1140+3del
  • LRG_300:g.67310del
  • NC_000017.10:g.59878611del
  • NM_032043.2:c.1140+3del
  • NM_032043.2:c.1140+3delG
Links:
dbSNP: rs2145331108
NCBI 1000 Genomes Browser:
rs2145331108
Molecular consequence:
  • NM_032043.3:c.1140+3del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001735971Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Dec 15, 2020)
germlineclinical testing

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

SCV002616975Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Likely pathogenic
(Jun 16, 2021)
germlineclinical testing

Citation Link

Summary from all submissions

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

Citations

PubMed

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]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001735971.1

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

Description

This variant causes a deletion at the +3 position of intron 8 of the BRIP1 gene. Splice site prediction tools suggest that this variant may have a significant impact on RNA splicing. However, this prediction has not been confirmed in published RNA studies. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

From Ambry Genetics, SCV002616975.2

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

Description

The c.1140+3delG intronic variant, located in intron 7 of the BRIP1 gene, results from a deletion of one nucleotide within intron 7 of the BRIP1 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Jan 19, 2025