rs34656552

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152743.4(BRAT1):c.1636G>T(p.Val546Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,611,718 control chromosomes in the GnomAD database, including 182 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 92 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 90 hom. )

Consequence

BRAT1
NM_152743.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.03

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00269109).

BP6

Variant 7-2539313-C-A is Benign according to our data. Variant chr7-2539313-C-A is described in ClinVar as [Benign]. Clinvar id is 472948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRAT1	NM_152743.4 link	c.1636G>T	p.Val546Leu	missense_variant	13/14	ENST00000340611.9	NP_689956.2	Q6PJG6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRAT1	ENST00000340611.9 link	c.1636G>T	p.Val546Leu	missense_variant	13/14	1	NM_152743.4	ENSP00000339637.4		Q6PJG6-1

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2741

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0629

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00642

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00438

AC:

1084

AN:

247410

Hom.:

AF XY:

0.00348

AC XY:

468

AN XY:

134550

show subpopulations

Gnomad AFR exome

AF:

0.0622

Gnomad AMR exome

AF:

0.00212

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00180

AC:

2625

AN:

1459476

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1152

AN XY:

725924

show subpopulations

Gnomad4 AFR exome

AF:

0.0647

Gnomad4 AMR exome

AF:

0.00311

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000558

Gnomad4 OTH exome

AF:

0.00387

GnomAD4 genome

AF:

0.0180

AC:

2744

AN:

152242

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1318

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0628

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00308

Hom.:

Bravo

AF:

0.0200

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0520

AC:

229

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00551

AC:

668

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -

BRAT1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 14, 2019

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

Feb 04, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.0

REVEL

Benign

0.10

Sift

Benign

0.16

Sift4G

Benign

0.18

Polyphen

0.98

Vest4

0.45

MutPred

0.29

Gain of helix (P = 0.132);

MVP

0.57

MPC

0.15

ClinPred

0.0072

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.066

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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