rs1043291

Variant names:

• chr7-2538147-T-C
• rs1043291
• NM_152743.4:c.2388A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-2538147-T-C
• chr7-2538147-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_152743.4(BRAT1):​c.2388A>G​(p.Glu796Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,607,532 control chromosomes in the GnomAD database, including 111,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (17030 hom., cov: 34)
  • Exomes 𝑓: 0.35 (94217 hom.)
• Consequence: BRAT1 NM_152743.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.444
• Publications: 18 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 7-2538147-T-C is Benign according to our data. Variant chr7-2538147-T-C is described in ClinVar as Benign. ClinVar VariationId is 585490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.444 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRAT1	NM_152743.4	MANE Select	c.2388A>G	p.Glu796Glu	synonymous	Exon 14 of 14	NP_689956.2	Q6PJG6-1
	BRAT1	NM_001350626.2		c.2568A>G	p.Glu856Glu	synonymous	Exon 14 of 14	NP_001337555.1
	BRAT1	NM_001350627.2		c.1863A>G	p.Glu621Glu	synonymous	Exon 13 of 13	NP_001337556.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRAT1	ENST00000340611.9	TSL:1 MANE Select	c.2388A>G	p.Glu796Glu	synonymous	Exon 14 of 14	ENSP00000339637.4	Q6PJG6-1
	BRAT1	ENST00000890463.1		c.2625A>G	p.Glu875Glu	synonymous	Exon 16 of 16	ENSP00000560522.1
	BRAT1	ENST00000917322.1		c.2622A>G	p.Glu874Glu	synonymous	Exon 16 of 16	ENSP00000587381.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68279 AN: 152070 Hom.: 16997 Cov.: 34

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.423

GnomAD2 exomes AF: 0.387 AC: 93845 AN: 242584 AF XY: 0.377

Gnomad AFR exome AF: 0.675

Gnomad AMR exome AF: 0.428

Gnomad ASJ exome AF: 0.297

Gnomad EAS exome AF: 0.359

Gnomad FIN exome AF: 0.483

Gnomad NFE exome AF: 0.345

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.354 AC: 514874 AN: 1455344 Hom.: 94217 Cov.: 54 AF XY: 0.351 AC XY: 254034 AN XY: 722856

African (AFR) AF: 0.680 AC: 22692 AN: 33392

American (AMR) AF: 0.429 AC: 19116 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 7752 AN: 26082

East Asian (EAS) AF: 0.364 AC: 14380 AN: 39530

South Asian (SAS) AF: 0.331 AC: 28462 AN: 86074

European-Finnish (FIN) AF: 0.476 AC: 24619 AN: 51714

Middle Eastern (MID) AF: 0.361 AC: 2074 AN: 5746

European-Non Finnish (NFE) AF: 0.337 AC: 373846 AN: 1108188

Other (OTH) AF: 0.365 AC: 21933 AN: 60056

GnomAD4 genome AF: 0.449 AC: 68366 AN: 152188 Hom.: 17030 Cov.: 34 AF XY: 0.451 AC XY: 33547 AN XY: 74404

African (AFR) AF: 0.670 AC: 27844 AN: 41534

American (AMR) AF: 0.421 AC: 6435 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 994 AN: 3472

East Asian (EAS) AF: 0.365 AC: 1885 AN: 5164

South Asian (SAS) AF: 0.336 AC: 1623 AN: 4824

European-Finnish (FIN) AF: 0.489 AC: 5186 AN: 10596

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22987 AN: 67978

Other (OTH) AF: 0.422 AC: 891 AN: 2112

Alfa AF: 0.387 Hom.: 5904

Bravo AF: 0.455

Asia WGS AF: 0.353 AC: 1227 AN: 3478

EpiCase AF: 0.337

EpiControl AF: 0.338

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Neonatal-onset encephalopathy with rigidity and seizures (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.5
DANN	Benign	0.43
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1043291; hg19: chr7-2577781; COSMIC: COSV61394529; COSMIC: COSV61394529;