rs201523118

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_152743.4(BRAT1):c.1792C>T(p.His598Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000136 in 1,598,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

BRAT1
NM_152743.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 3.80

Publications

1 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015027821).

BP6

Variant 7-2538743-G-A is Benign according to our data. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421. Variant chr7-2538743-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 566421.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAT1	NM_152743.4 link	c.1792C>T	p.His598Tyr	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.1792C>T	p.His598Tyr	missense_variant	Exon 14 of 14	1	NM_152743.4	ENSP00000339637.4		Q6PJG6-1

Frequencies

GnomAD3 genomes

AF:

0.000801

AC:

122

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00277

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000164

AC:

AN:

231904

AF XY:

0.000141

show subpopulations

Gnomad AFR exome

AF:

0.00208

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000512

GnomAD4 exome

AF:

0.0000664

AC:

AN:

1446042

Hom.:

Cov.:

AF XY:

0.0000445

AC XY:

AN XY:

719736

show subpopulations

African (AFR)

AF:

0.00215

AC:

AN:

33472

American (AMR)

AF:

0.000179

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37888

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111840

Other (OTH)

AF:

0.000216

AC:

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000801

AC:

122

AN:

152374

Hom.:

Cov.:

AF XY:

0.000765

AC XY:

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.00276

AC:

115

AN:

41600

American (AMR)

AF:

0.000327

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000304

Hom.:

Bravo

AF:

0.000850

ESP6500AA

AF:

0.000696

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000175

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:2Benign:1

Aug 20, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 18, 2020

Revvity Omics, Revvity

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 13, 2017

Athena Diagnostics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

BRAT1-related disorder

Benign:1

Jun 06, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Neonatal-onset encephalopathy with rigidity and seizures

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0072

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.69

M_CAP

Benign

0.024

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

3.8

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.9

REVEL

Benign

0.10

Sift

Benign

0.047

Sift4G

Benign

0.12

Polyphen

0.63

Vest4

0.25

MVP

0.25

MPC

0.087

ClinPred

0.030

GERP RS

2.5

Varity_R

0.035

gMVP

0.13

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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