7-2543273-C-T

Position:

• chr7-2543273-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152743.4(BRAT1):​c.854G>A​(p.Arg285Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 1,610,734 control chromosomes in the GnomAD database, including 2,175 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (272 hom., cov: 32)
  • Exomes 𝑓: 0.023 (1903 hom.)
• Consequence: BRAT1 NM_152743.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.94

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004017681).
• BP6: Variant 7-2543273-C-T is Benign according to our data. Variant chr7-2543273-C-T is described in ClinVar as [Benign]. Clinvar id is 472982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRAT1	NM_152743.4	c.854G>A	p.Arg285Gln	missense_variant	6/14	ENST00000340611.9	NP_689956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRAT1	ENST00000340611.9	c.854G>A	p.Arg285Gln	missense_variant	6/14	1	NM_152743.4	ENSP00000339637	P1

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3985 AN: 152128 Hom.: 277 Cov.: 32

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0397

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00969

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.0488 AC: 12097 AN: 247920 Hom.: 930 AF XY: 0.0497 AC XY: 6666 AN XY: 134224

Gnomad AFR exome AF: 0.00217

Gnomad AMR exome AF: 0.0416

Gnomad ASJ exome AF: 0.0207

Gnomad EAS exome AF: 0.276

Gnomad SAS exome AF: 0.0969

Gnomad FIN exome AF: 0.0526

Gnomad NFE exome AF: 0.0111

Gnomad OTH exome AF: 0.0348

GnomAD4 exome AF: 0.0227 AC: 33158 AN: 1458488 Hom.: 1903 Cov.: 31 AF XY: 0.0249 AC XY: 18032 AN XY: 725378

Gnomad4 AFR exome AF: 0.00237

Gnomad4 AMR exome AF: 0.0419

Gnomad4 ASJ exome AF: 0.0205

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.0953

Gnomad4 FIN exome AF: 0.0497

Gnomad4 NFE exome AF: 0.00770

Gnomad4 OTH exome AF: 0.0350

GnomAD4 genome AF: 0.0261 AC: 3973 AN: 152246 Hom.: 272 Cov.: 32 AF XY: 0.0309 AC XY: 2303 AN XY: 74440

Gnomad4 AFR AF: 0.00298

Gnomad4 AMR AF: 0.0397

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.00967

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0199 Hom.: 272

Bravo AF: 0.0236

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.00250 AC: 11

ESP6500EA AF: 0.00965 AC: 83

ExAC AF: 0.0488 AC: 5919

Asia WGS AF: 0.144 AC: 500 AN: 3478

EpiCase AF: 0.00988

EpiControl AF: 0.0109

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 21, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2018	- -

Neonatal-onset encephalopathy with rigidity and seizures Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.072
DANN	Benign	0.52
DEOGEN2	Benign	0.00092	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.40	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.21
Sift	Benign	1.0	T
Sift4G	Benign	0.69	T
Polyphen		0.0	B
Vest4		0.021
MPC		0.050
ClinPred		0.0064	T
GERP RS		-9.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.012
gMVP		0.036

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

Other links and lift over

dbSNP: rs77213198; hg19: chr7-2582907; COSMIC: COSV61394438; COSMIC: COSV61394438;