Variant rs2917726 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_152743.4(BRAT1):c.1923G>A(p.Ala641=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 1,597,516 control chromosomes in the GnomAD database, including 4,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 349 hom., cov: 34)

Exomes 𝑓: 0.060 ( 3855 hom. )

Consequence

BRAT1
NM_152743.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.460

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 7-2538612-C-T is Benign according to our data. Variant chr7-2538612-C-T is described in ClinVar as [Benign]. Clinvar id is 585488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 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.1923G>A	p.Ala641=	synonymous_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.1923G>A	p.Ala641=	synonymous_variant	14/14	1	NM_152743.4	P1	Q6PJG6-1

Frequencies

GnomAD3 genomes

AF:

0.0484

AC:

7365

AN:

152154

Hom.:

348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0721

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.0624

Gnomad FIN

AF:

0.0354

Gnomad MID

AF:

0.0701

Gnomad NFE

AF:

0.0505

Gnomad OTH

AF:

0.0497

GnomAD3 exomes

AF:

0.0680

AC:

15287

AN:

224900

Hom.:

893

AF XY:

0.0660

AC XY:

8266

AN XY:

125274

show subpopulations

Gnomad AFR exome

AF:

0.0104

Gnomad AMR exome

AF:

0.0783

Gnomad ASJ exome

AF:

0.0721

Gnomad EAS exome

AF:

0.248

Gnomad SAS exome

AF:

0.0557

Gnomad FIN exome

AF:

0.0307

Gnomad NFE exome

AF:

0.0499

Gnomad OTH exome

AF:

0.0546

GnomAD4 exome

AF:

0.0596

AC:

86198

AN:

1445244

Hom.:

3855

Cov.:

AF XY:

0.0593

AC XY:

42657

AN XY:

719450

show subpopulations

Gnomad4 AFR exome

AF:

0.00936

Gnomad4 AMR exome

AF:

0.0782

Gnomad4 ASJ exome

AF:

0.0726

Gnomad4 EAS exome

AF:

0.276

Gnomad4 SAS exome

AF:

0.0573

Gnomad4 FIN exome

AF:

0.0310

Gnomad4 NFE exome

AF:

0.0533

Gnomad4 OTH exome

AF:

0.0641

GnomAD4 genome

AF:

0.0484

AC:

7374

AN:

152272

Hom.:

349

Cov.:

AF XY:

0.0510

AC XY:

3799

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0124

Gnomad4 AMR

AF:

0.0724

Gnomad4 ASJ

AF:

0.0657

Gnomad4 EAS

AF:

0.248

Gnomad4 SAS

AF:

0.0626

Gnomad4 FIN

AF:

0.0354

Gnomad4 NFE

AF:

0.0505

Gnomad4 OTH

AF:

0.0501

Alfa

AF:

0.0500

Hom.:

Bravo

AF:

0.0504

Asia WGS

AF:

0.146

AC:

506

AN:

3478

EpiCase

AF:

0.0508

EpiControl

AF:

0.0489

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	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 21. Only high quality variants are reported. -

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

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.0

DANN

Benign

0.68

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