7-2538603-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.1932A>G(p.Arg644Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,597,032 control chromosomes in the GnomAD database, including 109,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R644R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.45 ( 16930 hom., cov: 33)

Exomes 𝑓: 0.35 ( 92648 hom. )

Consequence

BRAT1
NM_152743.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00800

Publications

13 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=-0.84).

BP6

Variant 7-2538603-T-C is Benign according to our data. Variant chr7-2538603-T-C is described in ClinVar as Benign. ClinVar VariationId is 585489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.008 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAT1	NM_152743.4 link	c.1932A>G	p.Arg644Arg	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.1932A>G	p.Arg644Arg	synonymous_variant	Exon 14 of 14	1	NM_152743.4	ENSP00000339637.4		Q6PJG6-1

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

68051

AN:

151896

Hom.:

16898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.668

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.489

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.421

GnomAD2 exomes

AF:

0.385

AC:

86750

AN:

225130

AF XY:

0.376

show subpopulations

Gnomad AFR exome

AF:

0.678

Gnomad AMR exome

AF:

0.430

Gnomad ASJ exome

AF:

0.299

Gnomad EAS exome

AF:

0.362

Gnomad FIN exome

AF:

0.492

Gnomad NFE exome

AF:

0.348

Gnomad OTH exome

AF:

0.370

GnomAD4 exome

AF:

0.353

AC:

509491

AN:

1445018

Hom.:

92648

Cov.:

AF XY:

0.350

AC XY:

252045

AN XY:

719226

show subpopulations

African (AFR)

AF:

0.677

AC:

22632

AN:

33426

American (AMR)

AF:

0.430

AC:

19038

AN:

44310

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

7753

AN:

26046

East Asian (EAS)

AF:

0.363

AC:

14389

AN:

39586

South Asian (SAS)

AF:

0.331

AC:

28452

AN:

86054

European-Finnish (FIN)

AF:

0.477

AC:

18792

AN:

39374

Middle Eastern (MID)

AF:

0.360

AC:

2074

AN:

5762

European-Non Finnish (NFE)

AF:

0.337

AC:

374456

AN:

1110390

Other (OTH)

AF:

0.365

AC:

21905

AN:

60070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

23985

47970

71955

95940

119925

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12218

24436

36654

48872

61090

<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:

0.448

AC:

68137

AN:

152014

Hom.:

16930

Cov.:

AF XY:

0.450

AC XY:

33438

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.668

AC:

27731

AN:

41504

American (AMR)

AF:

0.419

AC:

6402

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

993

AN:

3470

East Asian (EAS)

AF:

0.368

AC:

1887

AN:

5130

South Asian (SAS)

AF:

0.335

AC:

1619

AN:

4826

European-Finnish (FIN)

AF:

0.489

AC:

5169

AN:

10570

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.338

AC:

22932

AN:

67920

Other (OTH)

AF:

0.419

AC:

885

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1882

3764

5647

7529

9411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<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:

0.286

Hom.:

1169

Bravo

AF:

0.454

Asia WGS

AF:

0.352

AC:

1221

AN:

3478

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 61% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 57. Only high quality variants are reported. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Jul 17, 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

-0.84

CADD

Benign

6.2

(source)

DANN

Benign

0.42

PhyloP100

0.0080

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