rs61729932

Positions:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_152743.4(BRAT1):c.2353C>T(p.Arg785Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00401 in 1,609,228 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.0024 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0042 ( 28 hom. )

Consequence

BRAT1
NM_152743.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 1.64

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038573146).

BP6

Variant 7-2538182-G-A is Benign according to our data. Variant chr7-2538182-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 445886.We mark this variant Likely_benign, oryginal submissions are: {Benign=4, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRAT1	NM_152743.4 linkuse as main transcript	c.2353C>T	p.Arg785Trp	missense_variant	14/14	ENST00000340611.9	NP_689956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRAT1	ENST00000340611.9 linkuse as main transcript	c.2353C>T	p.Arg785Trp	missense_variant	14/14	1	NM_152743.4	ENSP00000339637	P1	Q6PJG6-1
BRAT1	ENST00000467558.5 linkuse as main transcript	n.4139C>T		non_coding_transcript_exon_variant	10/10	5
BRAT1	ENST00000469750.5 linkuse as main transcript	n.4925C>T		non_coding_transcript_exon_variant	11/11	2
BRAT1	ENST00000493232.5 linkuse as main transcript	n.5059C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00245

AC:

373

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00406

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00292

AC:

709

AN:

242482

Hom.:

AF XY:

0.00309

AC XY:

411

AN XY:

132880

show subpopulations

Gnomad AFR exome

AF:

0.000464

Gnomad AMR exome

AF:

0.000582

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000656

Gnomad FIN exome

AF:

0.00332

Gnomad NFE exome

AF:

0.00423

Gnomad OTH exome

AF:

0.00299

GnomAD4 exome

AF:

0.00417

AC:

6073

AN:

1456868

Hom.:

Cov.:

AF XY:

0.00412

AC XY:

2983

AN XY:

724126

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000515

Gnomad4 ASJ exome

AF:

0.0121

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000986

Gnomad4 FIN exome

AF:

0.00331

Gnomad4 NFE exome

AF:

0.00476

Gnomad4 OTH exome

AF:

0.00309

GnomAD4 genome

AF:

0.00245

AC:

373

AN:

152360

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

179

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000827

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00406

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00325

Hom.:

Bravo

AF:

0.00228

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000685

AC:

ESP6500EA

AF:

0.00445

AC:

ExAC

AF:

0.00283

AC:

343

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00387

EpiControl

AF:

0.00391

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	BRAT1: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 15, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 13, 2018	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 10, 2017	- -

Neonatal-onset encephalopathy with rigidity and seizures

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 27, 2024

- -

Intellectual disability

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

Jan 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.026

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.12

Sift

Uncertain

0.010

Sift4G

Uncertain

0.023

Polyphen

1.0

Vest4

0.28

MVP

0.38

MPC

0.18

ClinPred

0.018

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.062

gMVP

0.34

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