rs113030000

Variant names:

• chr7-2538613-G-A
• rs113030000
• NM_152743.4:c.1922C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-2538613-G-A
• chr7-2538613-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_152743.4(BRAT1):​c.1922C>T​(p.Ala641Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000377 in 1,595,332 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. A641A) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: BRAT1 NM_152743.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.350
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023168623).
• BP6: Variant 7-2538613-G-A is Benign according to our data. Variant chr7-2538613-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 472956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.1922C>T	p.Ala641Val	missense	Exon 14 of 14	NP_689956.2	Q6PJG6-1
	BRAT1	NM_001350626.2		c.2102C>T	p.Ala701Val	missense	Exon 14 of 14	NP_001337555.1
	BRAT1	NM_001350627.2		c.1397C>T	p.Ala466Val	missense	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.1922C>T	p.Ala641Val	missense	Exon 14 of 14	ENSP00000339637.4	Q6PJG6-1
	BRAT1	ENST00000890463.1		c.2159C>T	p.Ala720Val	missense	Exon 16 of 16	ENSP00000560522.1
	BRAT1	ENST00000917322.1		c.2156C>T	p.Ala719Val	missense	Exon 16 of 16	ENSP00000587381.1

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 291 AN: 152164 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.00680

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000540 AC: 119 AN: 220304 AF XY: 0.000399

Gnomad AFR exome AF: 0.00770

Gnomad AMR exome AF: 0.000330

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000581

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000300

Gnomad OTH exome AF: 0.000178

GnomAD4 exome AF: 0.000213 AC: 307 AN: 1443050 Hom.: 1 Cov.: 70 AF XY: 0.000189 AC XY: 136 AN XY: 718196

African (AFR) AF: 0.00686 AC: 229 AN: 33398

American (AMR) AF: 0.000409 AC: 18 AN: 44030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25976

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39410

South Asian (SAS) AF: 0.00 AC: 0 AN: 85870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38616

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5740

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1109976

Other (OTH) AF: 0.000650 AC: 39 AN: 60034

GnomAD4 genome AF: 0.00194 AC: 295 AN: 152282 Hom.: 1 Cov.: 34 AF XY: 0.00204 AC XY: 152 AN XY: 74456

African (AFR) AF: 0.00688 AC: 286 AN: 41566

American (AMR) AF: 0.000523 AC: 8 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000757 Hom.: 0

Bravo AF: 0.00222

ESP6500AA AF: 0.00640 AC: 27

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000663 AC: 79

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	BRAT1-related disorder (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	Neonatal-onset encephalopathy with rigidity and seizures (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.0080
DANN	Benign	0.17
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.35	T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	-0.28	N
PhyloP100		-0.35
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.065
MVP		0.048
MPC		0.046
ClinPred		0.0091	T
GERP RS		-11
Varity_R		0.022
gMVP		0.090
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs113030000; hg19: chr7-2578247;