7-2538147-T-C

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.2388A>G(p.Glu796Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,607,532 control chromosomes in the GnomAD database, including 111,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 17030 hom., cov: 34)

Exomes 𝑓: 0.35 ( 94217 hom. )

Consequence

BRAT1
NM_152743.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.444

Publications

18 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=-0.77).

BP6

Variant 7-2538147-T-C is Benign according to our data. Variant chr7-2538147-T-C is described in ClinVar as Benign. ClinVar VariationId is 585490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.444 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAT1	NM_152743.4 link	c.2388A>G	p.Glu796Glu	synonymous_variant	Exon 14 of 14	ENST00000340611.9	NP_689956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
BRAT1	ENST00000340611.9 link	c.2388A>G	p.Glu796Glu	synonymous_variant	Exon 14 of 14	1	NM_152743.4	ENSP00000339637.4
BRAT1	ENST00000467558.5 link	n.4174A>G		non_coding_transcript_exon_variant	Exon 10 of 10	5
BRAT1	ENST00000469750.5 link	n.4960A>G		non_coding_transcript_exon_variant	Exon 11 of 11	2
BRAT1	ENST00000493232.5 link	n.5094A>G		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68279

AN:

152070

Hom.:

16997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.670

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.420

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.489

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.423

GnomAD2 exomes

AF:

0.387

AC:

93845

AN:

242584

AF XY:

0.377

show subpopulations

Gnomad AFR exome

AF:

0.675

Gnomad AMR exome

AF:

0.428

Gnomad ASJ exome

AF:

0.297

Gnomad EAS exome

AF:

0.359

Gnomad FIN exome

AF:

0.483

Gnomad NFE exome

AF:

0.345

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.354

AC:

514874

AN:

1455344

Hom.:

94217

Cov.:

AF XY:

0.351

AC XY:

254034

AN XY:

722856

show subpopulations

African (AFR)

AF:

0.680

AC:

22692

AN:

33392

American (AMR)

AF:

0.429

AC:

19116

AN:

44562

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

7752

AN:

26082

East Asian (EAS)

AF:

0.364

AC:

14380

AN:

39530

South Asian (SAS)

AF:

0.331

AC:

28462

AN:

86074

European-Finnish (FIN)

AF:

0.476

AC:

24619

AN:

51714

Middle Eastern (MID)

AF:

0.361

AC:

2074

AN:

5746

European-Non Finnish (NFE)

AF:

0.337

AC:

373846

AN:

1108188

Other (OTH)

AF:

0.365

AC:

21933

AN:

60056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

21745

43489

65234

86978

108723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12226

24452

36678

48904

61130

<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:

0.449

AC:

68366

AN:

152188

Hom.:

17030

Cov.:

AF XY:

0.451

AC XY:

33547

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.670

AC:

27844

AN:

41534

American (AMR)

AF:

0.421

AC:

6435

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

994

AN:

3472

East Asian (EAS)

AF:

0.365

AC:

1885

AN:

5164

South Asian (SAS)

AF:

0.336

AC:

1623

AN:

4824

European-Finnish (FIN)

AF:

0.489

AC:

5186

AN:

10596

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.338

AC:

22987

AN:

67978

Other (OTH)

AF:

0.422

AC:

891

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1825

3651

5476

7302

9127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<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:

0.387

Hom.:

5904

Bravo

AF:

0.455

Asia WGS

AF:

0.353

AC:

1227

AN:

3478

EpiCase

AF:

0.337

EpiControl

AF:

0.338

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 60% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 56. Only high quality variants are reported.

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:2

Jul 07, 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

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

-0.77

CADD

Benign

1.5

(source)

DANN

Benign

0.43

PhyloP100

-0.44

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