7-2538612-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_152743.4(BRAT1):c.1923G>A(p.Ala641Ala) 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

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

neonatal-onset encephalopathy with rigidity and seizures
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder with cerebellar atrophy and with or without seizures
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics

BRAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
BRAT1	NM_152743.4 link	c.1923G>A	p.Ala641Ala	synonymous_variant	Exon 14 of 14	ENST00000340611.9	NP_689956.2	Q6PJG6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRAT1	ENST00000340611.9 link	c.1923G>A	p.Ala641Ala	synonymous_variant	Exon 14 of 14	1	NM_152743.4	ENSP00000339637.4		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

GnomAD2 exomes

AF:

0.0680

AC:

15287

AN:

224900

AF XY:

0.0660

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 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

African (AFR)

AF:

0.00936

AC:

313

AN:

33436

American (AMR)

AF:

0.0782

AC:

3479

AN:

44508

Ashkenazi Jewish (ASJ)

AF:

0.0726

AC:

1893

AN:

26058

East Asian (EAS)

AF:

0.276

AC:

10919

AN:

39604

South Asian (SAS)

AF:

0.0573

AC:

4929

AN:

86090

European-Finnish (FIN)

AF:

0.0310

AC:

1203

AN:

38866

Middle Eastern (MID)

AF:

0.0664

AC:

382

AN:

5756

European-Non Finnish (NFE)

AF:

0.0533

AC:

59227

AN:

1110848

Other (OTH)

AF:

0.0641

AC:

3853

AN:

60078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

5480

10960

16439

21919

27399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2404

4808

7212

9616

12020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0484

AC:

7374

AN:

152272

Hom.:

349

Cov.:

AF XY:

0.0510

AC XY:

3799

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0124

AC:

517

AN:

41570

American (AMR)

AF:

0.0724

AC:

1108

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

228

AN:

3470

East Asian (EAS)

AF:

0.248

AC:

1280

AN:

5160

South Asian (SAS)

AF:

0.0626

AC:

302

AN:

4822

European-Finnish (FIN)

AF:

0.0354

AC:

376

AN:

10622

Middle Eastern (MID)

AF:

0.0753

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0505

AC:

3435

AN:

67998

Other (OTH)

AF:

0.0501

AC:

106

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

362

723

1085

1446

1808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Jul 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.0

(source)

DANN

Benign

0.68

PhyloP100

-0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over