Variant 7-2538326-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152743.4(BRAT1):c.2209C>T(p.Arg737Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 1,613,002 control chromosomes in the GnomAD database, including 249 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 121 hom., cov: 34)

Exomes 𝑓: 0.0024 ( 128 hom. )

Consequence

BRAT1
NM_152743.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0380

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001966834).

BP6

Variant 7-2538326-G-A is Benign according to our data. Variant chr7-2538326-G-A is described in ClinVar as [Benign]. Clinvar id is 446897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRAT1	NM_152743.4 link	c.2209C>T	p.Arg737Trp	missense_variant	14/14	ENST00000340611.9	NP_689956.2	Q6PJG6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BRAT1	ENST00000340611.9 link	c.2209C>T	p.Arg737Trp	missense_variant	14/14	1	NM_152743.4	ENSP00000339637.4	Q6PJG6-1
BRAT1	ENST00000467558.5 link	n.3995C>T		non_coding_transcript_exon_variant	10/10	5
BRAT1	ENST00000469750.5 link	n.4781C>T		non_coding_transcript_exon_variant	11/11	2
BRAT1	ENST00000493232.5 link	n.4915C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3495

AN:

152196

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0782

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0205

GnomAD3 exomes

AF:

0.00594

AC:

1475

AN:

248252

Hom.:

AF XY:

0.00438

AC XY:

591

AN XY:

134812

show subpopulations

Gnomad AFR exome

AF:

0.0772

Gnomad AMR exome

AF:

0.00458

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000996

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000278

Gnomad OTH exome

AF:

0.00361

GnomAD4 exome

AF:

0.00241

AC:

3515

AN:

1460688

Hom.:

128

Cov.:

AF XY:

0.00211

AC XY:

1533

AN XY:

726670

show subpopulations

Gnomad4 AFR exome

AF:

0.0790

Gnomad4 AMR exome

AF:

0.00490

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.00681

GnomAD4 genome

AF:

0.0230

AC:

3499

AN:

152314

Hom.:

121

Cov.:

AF XY:

0.0222

AC XY:

1652

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0780

Gnomad4 AMR

AF:

0.0119

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.00569

Hom.:

Bravo

AF:

0.0262

ESP6500AA

AF:

0.0765

AC:

337

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00736

AC:

893

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jun 28, 2017

- -

Neonatal-onset encephalopathy with rigidity and seizures

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0022

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.1

REVEL

Benign

0.033

Sift

Benign

0.039

Sift4G

Uncertain

0.028

Polyphen

0.0030

Vest4

0.12

MVP

0.22

MPC

0.047

ClinPred

0.015

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over