NM_032043.3(BRIP1):c.3390_3393del (p.Tyr1131fs) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 29, 2024
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:: RCV000543566.13

Allele description [Variation Report for NM_032043.3(BRIP1):c.3390_3393del (p.Tyr1131fs)]

NM_032043.3(BRIP1):c.3390_3393del (p.Tyr1131fs)

Gene:

BRIP1:BRCA1 interacting DNA helicase 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

17q23.2

Genomic location:

Preferred name:

NM_032043.3(BRIP1):c.3390_3393del (p.Tyr1131fs)

HGVS:

NC_000017.11:g.61683655AGAT[1]
NG_007409.2:g.184900CTAT[1]
NM_032043.3:c.3390_3393delMANE SELECT
NP_114432.2:p.Tyr1131fs
LRG_300t1:c.3390_3393del
LRG_300:g.184900CTAT[1]
NC_000017.10:g.59761014_59761017del
NC_000017.10:g.59761016AGAT[1]
NM_032043.2:c.3390_3393del
NM_032043.2:c.3390_3393delCTAT

Protein change:

Y1131fs

Links:

dbSNP: rs778664039

NCBI 1000 Genomes Browser:

rs778664039

Molecular consequence:

NM_032043.3:c.3390_3393del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial; Hereditary breast cancer
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

Name:: Fanconi anemia complementation group J
Identifiers:: MONDO: MONDO:0012187; MedGen: C1836860; Orphanet: 84; OMIM: 609054

Recent activity

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NADH dehydrogenase subunit 6 (mitochondrion) [Fulmarus glacialis]
NADH dehydrogenase subunit 6 (mitochondrion) [Fulmarus glacialis]
gi|1910804045|gb|QOD97298.1|

Protein
Huang Qi [Supplementary Concept]
Huang Qi [Supplementary Concept]
Root extract preparation from Astragalus propinquus that is used in traditional Chinese medicine and is thought to posses anti-ageing properties.<br/>Date introduced: January 12, 1981<br/>

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000633669	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 29, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27701467, 20159562, 21127055, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000633669

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 29, 2024)

germline

clinical testing

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

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline Variants of Prostate Cancer in Japanese Families.

Hayano T, Matsui H, Nakaoka H, Ohtake N, Hosomichi K, Suzuki K, Inoue I.

PLoS One. 2016;11(10):e0164233. doi: 10.1371/journal.pone.0164233.

PubMed [citation]

PMID:: 27701467
PMCID:: PMC5049788

BACH1/FANCJ acts with TopBP1 and participates early in DNA replication checkpoint control.

Gong Z, Kim JE, Leung CC, Glover JN, Chen J.

Mol Cell. 2010 Feb 12;37(3):438-46. doi: 10.1016/j.molcel.2010.01.002.

PubMed [citation]

PMID:: 20159562
PMCID:: PMC3695484

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000633669.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Tyr1131Leufs*18) in the BRIP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 119 amino acid(s) of the BRIP1 protein. This variant is present in population databases (rs778664039, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with prostate cancer (PMID: 27701467). This variant is also known as p.I1130fs. ClinVar contains an entry for this variant (Variation ID: 229712). This variant disrupts the TopBP1-binding region of the BRIP1 protein, which plays a critical role in RPA chromatin loading and the activation of the replication checkpoint in response to DNA damage (PMID: 20159562, 21127055). While functional studies have not been performed to directly test the effect of this variant on BRIP1 protein function, this suggests that disruption of this region of the protein is causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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