Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000340611.9(BRAT1):c.675C>T(p.Phe225Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000748 in 1,586,200 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 3 hom. )

Consequence

BRAT1
ENST00000340611.9 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0920

Publications

0 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=-0.78).

BP6

Variant 7-2543718-G-A is Benign according to our data. Variant chr7-2543718-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 434519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.092 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00397 (605/152356) while in subpopulation AFR AF = 0.0135 (562/41590). AF 95% confidence interval is 0.0126. There are 4 homozygotes in GnomAd4. There are 286 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000340611.9. 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.675C>T	p.Phe225Phe	synonymous	Exon 5 of 14	NP_689956.2
BRAT1	NM_001350626.2		c.675C>T	p.Phe225Phe	synonymous	Exon 5 of 14	NP_001337555.1
BRAT1	NM_001350627.2		c.150C>T	p.Phe50Phe	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.675C>T	p.Phe225Phe	synonymous	Exon 5 of 14	ENSP00000339637.4
BRAT1	ENST00000421712.1	TSL:3	n.*20C>T		non_coding_transcript_exon	Exon 3 of 5	ENSP00000409209.2
BRAT1	ENST00000467558.5	TSL:5	n.691C>T		non_coding_transcript_exon	Exon 4 of 10

Frequencies

GnomAD3 genomes

AF:

0.00399

AC:

608

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00103

AC:

246

AN:

239184

AF XY:

0.000781

show subpopulations

Gnomad AFR exome

AF:

0.0130

Gnomad AMR exome

AF:

0.000993

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000186

Gnomad OTH exome

AF:

0.000348

GnomAD4 exome

AF:

0.000406

AC:

582

AN:

1433844

Hom.:

Cov.:

AF XY:

0.000374

AC XY:

265

AN XY:

708458

show subpopulations

African (AFR)

AF:

0.0133

AC:

439

AN:

33002

American (AMR)

AF:

0.000922

AC:

AN:

43388

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25028

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39046

South Asian (SAS)

AF:

0.0000475

AC:

AN:

84284

European-Finnish (FIN)

AF:

0.0000193

AC:

AN:

51940

Middle Eastern (MID)

AF:

0.000707

AC:

AN:

5658

European-Non Finnish (NFE)

AF:

0.0000320

AC:

AN:

1092486

Other (OTH)

AF:

0.000983

AC:

AN:

59012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

110

147

184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00397

AC:

605

AN:

152356

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

286

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0135

AC:

562

AN:

41590

American (AMR)

AF:

0.00176

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68040

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

123

154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00187

Hom.:

Bravo

AF:

0.00448

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely 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)

Neonatal-onset encephalopathy with rigidity and seizures;C4748032:Neurodevelopmental disorder with cerebellar atrophy and with or without seizures (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.0

(source)

DANN

Benign

0.58

PhyloP100

-0.092

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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.

rs139443843

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