rs147745609

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_152743.4(BRAT1):c.1507C>T(p.Pro503Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00094 in 1,594,350 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P503L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00096 ( 1 hom. )

Consequence

BRAT1
NM_152743.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:6

Conservation

PhyloP100: 1.24

Publications

5 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 -1 ACMG points.

BP6

Variant 7-2539634-G-A is Benign according to our data. Variant chr7-2539634-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 472946.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAT1	NM_152743.4 link	c.1507C>T	p.Pro503Ser	missense_variant	Exon 12 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.1507C>T	p.Pro503Ser	missense_variant	Exon 12 of 14	1	NM_152743.4	ENSP00000339637.4		Q6PJG6-1

Frequencies

GnomAD3 genomes

AF:

0.000762

AC:

116

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000976

AC:

211

AN:

216204

AF XY:

0.00121

show subpopulations

Gnomad AFR exome

AF:

0.0000764

Gnomad AMR exome

AF:

0.000222

Gnomad ASJ exome

AF:

0.000428

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000542

Gnomad NFE exome

AF:

0.00108

Gnomad OTH exome

AF:

0.00236

GnomAD4 exome

AF:

0.000959

AC:

1383

AN:

1442048

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

761

AN XY:

715596

show subpopulations

African (AFR)

AF:

0.000182

AC:

AN:

33010

American (AMR)

AF:

0.000378

AC:

AN:

42340

Ashkenazi Jewish (ASJ)

AF:

0.000194

AC:

AN:

25722

East Asian (EAS)

AF:

0.00

AC:

AN:

38612

South Asian (SAS)

AF:

0.00289

AC:

241

AN:

83432

European-Finnish (FIN)

AF:

0.000174

AC:

AN:

51860

Middle Eastern (MID)

AF:

0.00593

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.000915

AC:

1008

AN:

1101762

Other (OTH)

AF:

0.00107

AC:

AN:

59572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

146

219

292

365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

108

144

180

<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:

0.000762

AC:

116

AN:

152302

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41554

American (AMR)

AF:

0.000261

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00116

AC:

AN:

68026

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.000910

Hom.:

Bravo

AF:

0.000816

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000815

AC:

ExAC

AF:

0.000985

AC:

119

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:2Benign:3

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BRAT1: BP4 -

Mar 16, 2022

Revvity Omics, Revvity

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 28, 2017

Athena Diagnostics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 18, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

BRAT1-related disorder

Benign:1

Feb 05, 2021

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 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Intellectual disability

Benign:1

Jan 01, 2019

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.040

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.61

M_CAP

Benign

0.083

MetaRNN

Benign

0.0089

MetaSVM

Benign

-0.72

MutationAssessor

Benign

2.0

PhyloP100

1.2

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.16

Sift

Benign

0.13

Sift4G

Benign

0.37

Polyphen

0.015

Vest4

0.14

MVP

0.36

MPC

0.075

ClinPred

0.019

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.18

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.40

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.40

Position offset: -12

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