NM_032043.3(BRIP1):c.3328G>T (p.Glu1110Ter) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 12, 2023
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:: RCV000465286.10

Allele description [Variation Report for NM_032043.3(BRIP1):c.3328G>T (p.Glu1110Ter)]

NM_032043.3(BRIP1):c.3328G>T (p.Glu1110Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

17q23.2

Genomic location:

Preferred name:

NM_032043.3(BRIP1):c.3328G>T (p.Glu1110Ter)

HGVS:

NC_000017.11:g.61683718C>A
NG_007409.2:g.184842G>T
NM_032043.3:c.3328G>TMANE SELECT
NP_114432.2:p.Glu1110Ter
NP_114432.2:p.Glu1110Ter
LRG_300t1:c.3328G>T
LRG_300:g.184842G>T
LRG_300p1:p.Glu1110Ter
NC_000017.10:g.59761079C>A
NM_032043.2:c.3328G>T

Protein change:

E1110*

Links:

dbSNP: rs1060501774

NCBI 1000 Genomes Browser:

rs1060501774

Molecular consequence:

NM_032043.3:c.3328G>T - nonsense - [Sequence Ontology: SO:0001587]

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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000547367	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 12, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20159562, 21127055, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000547367

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 12, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

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

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

Molecular basis of BACH1/FANCJ recognition by TopBP1 in DNA replication checkpoint control.

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

J Biol Chem. 2011 Feb 11;286(6):4292-301. doi: 10.1074/jbc.M110.189555. Epub 2010 Dec 2.

PubMed [citation]

PMID:: 21127055
PMCID:: PMC3039391

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000547367.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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. 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. ClinVar contains an entry for this variant (Variation ID: 407865). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu1110*) in the BRIP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 140 amino acid(s) of the BRIP1 protein.

#	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 8, 2024

ClinVar

Relating variation to medicine