chr7-2542173-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_152743.4(BRAT1):c.962T>G(p.Leu321Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00838 in 1,571,350 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L321L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0066 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 60 hom. )

Consequence

BRAT1
NM_152743.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.39

Publications

11 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, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P
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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020496815).

BP6

Variant 7-2542173-A-C is Benign according to our data. Variant chr7-2542173-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 377093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152743.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRAT1	NM_152743.4	MANE Select	c.962T>G	p.Leu321Arg	missense	Exon 7 of 14	NP_689956.2	Q6PJG6-1
BRAT1	NM_001350626.2		c.962T>G	p.Leu321Arg	missense	Exon 7 of 14	NP_001337555.1
BRAT1	NM_001350627.2		c.437T>G	p.Leu146Arg	missense	Exon 6 of 13	NP_001337556.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRAT1	ENST00000340611.9	TSL:1 MANE Select	c.962T>G	p.Leu321Arg	missense	Exon 7 of 14	ENSP00000339637.4	Q6PJG6-1
BRAT1	ENST00000890463.1		c.962T>G	p.Leu321Arg	missense	Exon 7 of 16	ENSP00000560522.1
BRAT1	ENST00000917322.1		c.959T>G	p.Leu320Arg	missense	Exon 7 of 16	ENSP00000587381.1

Frequencies

GnomAD3 genomes

AF:

0.00660

AC:

1003

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00374

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00931

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00598

AC:

1104

AN:

184708

AF XY:

0.00611

show subpopulations

Gnomad AFR exome

AF:

0.000658

Gnomad AMR exome

AF:

0.00365

Gnomad ASJ exome

AF:

0.00344

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00927

Gnomad NFE exome

AF:

0.00816

Gnomad OTH exome

AF:

0.00677

GnomAD4 exome

AF:

0.00857

AC:

12165

AN:

1419238

Hom.:

Cov.:

AF XY:

0.00857

AC XY:

6018

AN XY:

702068

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

32558

American (AMR)

AF:

0.00394

AC:

152

AN:

38582

Ashkenazi Jewish (ASJ)

AF:

0.00372

AC:

AN:

25292

East Asian (EAS)

AF:

0.00

AC:

AN:

37576

South Asian (SAS)

AF:

0.00624

AC:

504

AN:

80752

European-Finnish (FIN)

AF:

0.00855

AC:

425

AN:

49700

Middle Eastern (MID)

AF:

0.00771

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.00963

AC:

10503

AN:

1090266

Other (OTH)

AF:

0.00697

AC:

410

AN:

58802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

642

1284

1927

2569

3211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

418

836

1254

1672

2090

<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:

0.00659

AC:

1002

AN:

152112

Hom.:

Cov.:

AF XY:

0.00629

AC XY:

468

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.00162

AC:

AN:

41482

American (AMR)

AF:

0.00765

AC:

117

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00374

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0106

AC:

113

AN:

10612

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00930

AC:

632

AN:

67952

Other (OTH)

AF:

0.00568

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

107

161

214

268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00728

Hom.:

Bravo

AF:

0.00600

ESP6500AA

AF:

0.00161

AC:

ESP6500EA

AF:

0.00643

AC:

ExAC

AF:

0.00370

AC:

439

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (6)

BRAT1-related disorder (1)

Neonatal-onset encephalopathy with rigidity and seizures (1)

Neonatal-onset encephalopathy with rigidity and seizures;C4748032:Neurodevelopmental disorder with cerebellar atrophy and with or without seizures (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.0084

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

MetaRNN

Benign

0.020

MetaSVM

Uncertain

0.084

MutationAssessor

Uncertain

2.5

PhyloP100

2.4

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.3

REVEL

Pathogenic

0.80

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.92

MVP

0.78

MPC

0.35

ClinPred

0.019

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.79

gMVP

0.85

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over