Variant rs56727079 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152743.4(BRAT1):c.1798C>T(p.Leu600Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,598,400 control chromosomes in the GnomAD database, including 2,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 335 hom., cov: 34)

Exomes 𝑓: 0.024 ( 1998 hom. )

Consequence

BRAT1
NM_152743.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.73

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=0.0017509162).

BP6

Variant 7-2538737-G-A is Benign according to our data. Variant chr7-2538737-G-A is described in ClinVar as [Benign]. Clinvar id is 585487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRAT1	NM_152743.4 linkuse as main transcript	c.1798C>T	p.Leu600Phe	missense_variant	14/14	ENST00000340611.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRAT1	ENST00000340611.9 linkuse as main transcript	c.1798C>T	p.Leu600Phe	missense_variant	14/14	1	NM_152743.4	P1	Q6PJG6-1

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

6278

AN:

152232

Hom.:

340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0542

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0463

Gnomad ASJ

AF:

0.0181

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.0516

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00995

Gnomad OTH

AF:

0.0435

GnomAD3 exomes

AF:

0.0548

AC:

12717

AN:

232088

Hom.:

973

AF XY:

0.0545

AC XY:

6974

AN XY:

127972

show subpopulations

Gnomad AFR exome

AF:

0.0557

Gnomad AMR exome

AF:

0.0462

Gnomad ASJ exome

AF:

0.0217

Gnomad EAS exome

AF:

0.282

Gnomad SAS exome

AF:

0.100

Gnomad FIN exome

AF:

0.0522

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.0372

GnomAD4 exome

AF:

0.0243

AC:

35163

AN:

1446050

Hom.:

1998

Cov.:

AF XY:

0.0264

AC XY:

18984

AN XY:

719742

show subpopulations

Gnomad4 AFR exome

AF:

0.0561

Gnomad4 AMR exome

AF:

0.0466

Gnomad4 ASJ exome

AF:

0.0209

Gnomad4 EAS exome

AF:

0.230

Gnomad4 SAS exome

AF:

0.0967

Gnomad4 FIN exome

AF:

0.0484

Gnomad4 NFE exome

AF:

0.00782

Gnomad4 OTH exome

AF:

0.0396

GnomAD4 genome

AF:

0.0412

AC:

6271

AN:

152350

Hom.:

335

Cov.:

AF XY:

0.0453

AC XY:

3375

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0542

Gnomad4 AMR

AF:

0.0463

Gnomad4 ASJ

AF:

0.0181

Gnomad4 EAS

AF:

0.269

Gnomad4 SAS

AF:

0.110

Gnomad4 FIN

AF:

0.0516

Gnomad4 NFE

AF:

0.00994

Gnomad4 OTH

AF:

0.0430

Alfa

AF:

0.0247

Hom.:

391

Bravo

AF:

0.0411

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.0390

AC:

168

ESP6500EA

AF:

0.00926

AC:

ExAC

AF:

0.0529

AC:

6363

Asia WGS

AF:

0.149

AC:

516

AN:

3478

EpiCase

AF:

0.0101

EpiControl

AF:

0.0110

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Sep 21, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2018	- -

Neonatal-onset encephalopathy with rigidity and seizures

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

0.0021

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.7

REVEL

Uncertain

0.36

Sift

Uncertain

0.0070

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.76

MPC

0.33

ClinPred

0.020

GERP RS

5.4

Varity_R

0.12

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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