rs56727079

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

12 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 -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 rank	MANE	Protein	UniProt
BRAT1	NM_152743.4 link	c.1798C>T	p.Leu600Phe	missense_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.1798C>T	p.Leu600Phe	missense_variant	Exon 14 of 14	1	NM_152743.4	ENSP00000339637.4		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

GnomAD2 exomes

AF:

0.0548

AC:

12717

AN:

232088

AF XY:

0.0545

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 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

African (AFR)

AF:

0.0561

AC:

1876

AN:

33470

American (AMR)

AF:

0.0466

AC:

2082

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0209

AC:

546

AN:

26126

East Asian (EAS)

AF:

0.230

AC:

9128

AN:

39692

South Asian (SAS)

AF:

0.0967

AC:

8341

AN:

86258

European-Finnish (FIN)

AF:

0.0484

AC:

1835

AN:

37896

Middle Eastern (MID)

AF:

0.0468

AC:

270

AN:

5766

European-Non Finnish (NFE)

AF:

0.00782

AC:

8695

AN:

1111842

Other (OTH)

AF:

0.0396

AC:

2390

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

2241

4482

6723

8964

11205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

552

1104

1656

2208

2760

<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:

0.0412

AC:

6271

AN:

152350

Hom.:

335

Cov.:

AF XY:

0.0453

AC XY:

3375

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.0542

AC:

2255

AN:

41594

American (AMR)

AF:

0.0463

AC:

709

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0181

AC:

AN:

3472

East Asian (EAS)

AF:

0.269

AC:

1390

AN:

5170

South Asian (SAS)

AF:

0.110

AC:

531

AN:

4832

European-Finnish (FIN)

AF:

0.0516

AC:

548

AN:

10614

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00994

AC:

676

AN:

68038

Other (OTH)

AF:

0.0430

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

289

578

867

1156

1445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0254

Hom.:

748

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

Sep 21, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 21, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Neonatal-onset encephalopathy with rigidity and seizures

Benign:1

Feb 03, 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

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

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

PhyloP100

2.7

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

Mutation Taster

=77/23

polymorphism (auto)

(source)

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

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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