Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_152743.4(BRAT1):c.699G>A(p.Thr233Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,569,366 control chromosomes in the GnomAD database, including 31,752 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2278 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29474 hom. )

Consequence

BRAT1
NM_152743.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.22

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

neonatal-onset encephalopathy with rigidity and seizures
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder with cerebellar atrophy and with or without seizures
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics

BRAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 7-2543694-C-T is Benign according to our data. Variant chr7-2543694-C-T is described in ClinVar as Benign. ClinVar VariationId is 585492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BRAT1	NM_152743.4	MANE Select	c.699G>A	p.Thr233Thr	synonymous	Exon 5 of 14	NP_689956.2
BRAT1	NM_001350626.2		c.699G>A	p.Thr233Thr	synonymous	Exon 5 of 14	NP_001337555.1
BRAT1	NM_001350627.2		c.174G>A	p.Thr58Thr	synonymous	Exon 4 of 13	NP_001337556.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BRAT1	ENST00000340611.9	TSL:1 MANE Select	c.699G>A	p.Thr233Thr	synonymous	Exon 5 of 14	ENSP00000339637.4
BRAT1	ENST00000421712.1	TSL:3	n.*44G>A		non_coding_transcript_exon	Exon 3 of 5	ENSP00000409209.2
BRAT1	ENST00000467558.5	TSL:5	n.715G>A		non_coding_transcript_exon	Exon 4 of 10

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23120

AN:

152116

Hom.:

2270

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0414

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.151

GnomAD2 exomes

AF:

0.175

AC:

39580

AN:

226326

AF XY:

0.177

show subpopulations

Gnomad AFR exome

AF:

0.0362

Gnomad AMR exome

AF:

0.205

Gnomad ASJ exome

AF:

0.155

Gnomad EAS exome

AF:

0.00231

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.189

GnomAD4 exome

AF:

0.197

AC:

279673

AN:

1417132

Hom.:

29474

Cov.:

AF XY:

0.196

AC XY:

136937

AN XY:

698142

show subpopulations

African (AFR)

AF:

0.0342

AC:

1116

AN:

32644

American (AMR)

AF:

0.205

AC:

8550

AN:

41638

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

3679

AN:

23864

East Asian (EAS)

AF:

0.00136

AC:

AN:

38838

South Asian (SAS)

AF:

0.160

AC:

12985

AN:

81372

European-Finnish (FIN)

AF:

0.244

AC:

12483

AN:

51226

Middle Eastern (MID)

AF:

0.138

AC:

767

AN:

5576

European-Non Finnish (NFE)

AF:

0.212

AC:

229643

AN:

1083620

Other (OTH)

AF:

0.178

AC:

10397

AN:

58354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

14664

29328

43991

58655

73319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7952

15904

23856

31808

39760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.152

AC:

23141

AN:

152234

Hom.:

2278

Cov.:

AF XY:

0.152

AC XY:

11324

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0416

AC:

1728

AN:

41566

American (AMR)

AF:

0.191

AC:

2919

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

515

AN:

3470

East Asian (EAS)

AF:

0.00347

AC:

AN:

5180

South Asian (SAS)

AF:

0.154

AC:

744

AN:

4826

European-Finnish (FIN)

AF:

0.248

AC:

2631

AN:

10596

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.208

AC:

14110

AN:

67990

Other (OTH)

AF:

0.151

AC:

318

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

990

1980

2970

3960

4950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.177

Hom.:

1068

Bravo

AF:

0.142

Asia WGS

AF:

0.0810

AC:

279

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Neonatal-onset encephalopathy with rigidity and seizures (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.22

(source)

DANN

Benign

0.72

PhyloP100

-3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_152743.4:c.699G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over