rs150942467

Positions:

chr7-2542173-A-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_152743.4(BRAT1):c.962T>G(p.Leu321Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00838 in 1,571,350 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 60 hom. )

Consequence

BRAT1
NM_152743.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.39

Variant links:

Genes affected

BRAT1 (HGNC:21701): (BRCA1 associated ATM activator 1) The protein encoded by this ubiquitously expressed gene interacts with the tumor suppressing BRCA1 (breast cancer 1) protein and and the ATM (ataxia telangiectasia mutated) protein. ATM is thought to be a master controller of cell cycle checkpoint signalling pathways that are required for cellular responses to DNA damage such as double-strand breaks that are induced by ionizing radiation and complexes with BRCA1 in the multi-protein complex BASC (BRAC1-associated genome surveillance complex). The protein encoded by this gene is thought to play a role in the DNA damage pathway regulated by BRCA1 and ATM. [provided by RefSeq, Mar 2012]

BRAT1 links:

BRAT1 (HGNC:):

BRAT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020496815).

BP6

Variant 7-2542173-A-C is Benign according to our data. Variant chr7-2542173-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 377093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-2542173-A-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRAT1	NM_152743.4 linkuse as main transcript	c.962T>G	p.Leu321Arg	missense_variant	7/14	ENST00000340611.9	NP_689956.2	Q6PJG6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRAT1	ENST00000340611.9 linkuse as main transcript	c.962T>G	p.Leu321Arg	missense_variant	7/14	1	NM_152743.4	ENSP00000339637.4		Q6PJG6-1

Frequencies

GnomAD3 genomes

AF:

0.00660

AC:

1003

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00374

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00931

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00598

AC:

1104

AN:

184708

Hom.:

AF XY:

0.00611

AC XY:

603

AN XY:

98702

show subpopulations

Gnomad AFR exome

AF:

0.000658

Gnomad AMR exome

AF:

0.00365

Gnomad ASJ exome

AF:

0.00344

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00584

Gnomad FIN exome

AF:

0.00927

Gnomad NFE exome

AF:

0.00816

Gnomad OTH exome

AF:

0.00677

GnomAD4 exome

AF:

0.00857

AC:

12165

AN:

1419238

Hom.:

Cov.:

AF XY:

0.00857

AC XY:

6018

AN XY:

702068

show subpopulations

Gnomad4 AFR exome

AF:

0.00101

Gnomad4 AMR exome

AF:

0.00394

Gnomad4 ASJ exome

AF:

0.00372

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00624

Gnomad4 FIN exome

AF:

0.00855

Gnomad4 NFE exome

AF:

0.00963

Gnomad4 OTH exome

AF:

0.00697

GnomAD4 genome

AF:

0.00659

AC:

1002

AN:

152112

Hom.:

Cov.:

AF XY:

0.00629

AC XY:

468

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00162

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00374

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.00930

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00729

Hom.:

Bravo

AF:

0.00600

ESP6500AA

AF:

0.00161

AC:

ESP6500EA

AF:

0.00643

AC:

ExAC

AF:

0.00370

AC:

439

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	BRAT1: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 12, 2016	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 14, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 23, 2020	This variant is associated with the following publications: (PMID: 29375859) -

BRAT1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 13, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Neonatal-onset encephalopathy with rigidity and seizures

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Neonatal-onset encephalopathy with rigidity and seizures;C4748032:Neurodevelopmental disorder with cerebellar atrophy and with or without seizures

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.0084

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

MetaRNN

Benign

0.020

MetaSVM

Uncertain

0.084

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.3

REVEL

Pathogenic

0.80

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.92

MVP

0.78

MPC

0.35

ClinPred

0.019

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.79

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over