NM_032043.3(BRIP1):c.3378A>C (p.Glu1126Asp) AND not provided

Germline classification:: Benign (2 submissions)
Last evaluated:: Jun 26, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000587193.7

Allele description [Variation Report for NM_032043.3(BRIP1):c.3378A>C (p.Glu1126Asp)]

NM_032043.3(BRIP1):c.3378A>C (p.Glu1126Asp)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

17q23.2

Genomic location:

Preferred name:

NM_032043.3(BRIP1):c.3378A>C (p.Glu1126Asp)

Other names:

p.E1126D:GAA>GAC

HGVS:

NC_000017.11:g.61683668T>G
NG_007409.2:g.184892A>C
NM_032043.3:c.3378A>CMANE SELECT
NP_114432.2:p.Glu1126Asp
NP_114432.2:p.Glu1126Asp
LRG_300t1:c.3378A>C
LRG_300:g.184892A>C
LRG_300p1:p.Glu1126Asp
NC_000017.10:g.59761029T>G
NM_032043.2:c.3378A>C
NM_032043.3:c.3378A>C
p.E1126D

Protein change:

E1126D

Links:

dbSNP: rs145855459

NCBI 1000 Genomes Browser:

rs145855459

Molecular consequence:

NM_032043.3:c.3378A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV000699720	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Aug 8, 2016)	germline	clinical testing	LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV001134025	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Benign (Jun 26, 2023)	unknown	clinical testing	PubMed (7) [See all records that cite these PMIDs] 27978560, 36315513, 25980754, 28503720, 24123366, 26921362, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000699720

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Aug 8, 2016)

germline

clinical testing

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV001134025

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Benign
(Jun 26, 2023)

unknown

clinical testing

PubMed (7)
[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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer.

Pearlman R, Frankel WL, Swanson B, Zhao W, Yilmaz A, Miller K, Bacher J, Bigley C, Nelsen L, Goodfellow PJ, Goldberg RM, Paskett E, Shields PG, Freudenheim JL, Stanich PP, Lattimer I, Arnold M, Liyanarachchi S, Kalady M, Heald B, Greenwood C, Paquette I, et al.

JAMA Oncol. 2017 Apr 1;3(4):464-471. doi: 10.1001/jamaoncol.2016.5194.

PubMed [citation]

PMID:: 27978560
PMCID:: PMC5564179

Hereditary variants of unknown significance in African American women with breast cancer.

McDonald JT, Ricks-Santi LJ.

PLoS One. 2022;17(10):e0273835. doi: 10.1371/journal.pone.0273835.

PubMed [citation]

PMID:: 36315513
PMCID:: PMC9621418

See all PubMed Citations (7)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699720.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: The BRIP1 c.3378A>C (p.Glu1126Asp) variant involves the alteration of a non-conserved nucleotide. 4/5 in silico tools predict a benign outcome for this variant . This variant was found in 26/121034 control chromosomes (1 homozygote), predominantly observed in the African subpopulation at a frequency of 0.002549 (26/10200). This frequency is about 41 times the estimated maximal expected allele frequency of a pathogenic BRIP1 variant (0.0000625), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, one clinical diagnostic laboratory classified this variant as uncertain significance and another lab classified this variant as likely benign, all without evidence to independently evaluate. One internal sample also carried a pathogenic variant in RAD51C gene, further supporting the benign classification of the variant of interest. Taken together, this variant is classified as benign.

#	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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001134025.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

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

Last Updated: Nov 10, 2024

ClinVar

Relating variation to medicine