rs3918143

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_005104.4(BRD2):c.1421C>T(p.Ala474Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,613,002 control chromosomes in the GnomAD database, including 859 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.024 ( 63 hom., cov: 32)

Exomes 𝑓: 0.031 ( 796 hom. )

Consequence

BRD2
NM_005104.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.50

Publications

23 publications found

Variant links:

Genes affected

BRD2 (HGNC:1103): (bromodomain containing 2) This gene encodes a transcriptional regulator that belongs to the BET (bromodomains and extra terminal domain) family of proteins. This protein associates with transcription complexes and with acetylated chromatin during mitosis, and it selectively binds to the acetylated lysine-12 residue of histone H4 via its two bromodomains. The gene maps to the major histocompatability complex (MHC) class II region on chromosome 6p21.3, but sequence comparison suggests that the protein is not involved in the immune response. This gene has been implicated in juvenile myoclonic epilepsy, a common form of epilepsy that becomes apparent in adolescence. Multiple alternatively spliced variants have been described for this gene. [provided by RefSeq, Dec 2010]

BRD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033878982).

BP6

Variant 6-32977848-C-T is Benign according to our data. Variant chr6-32977848-C-T is described in ClinVar as Benign. ClinVar VariationId is 3055955.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0236 (3597/152196) while in subpopulation SAS AF = 0.0388 (187/4818). AF 95% confidence interval is 0.0343. There are 63 homozygotes in GnomAd4. There are 1720 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 63 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD2	NM_005104.4 link	c.1421C>T	p.Ala474Val	missense_variant	Exon 9 of 13	ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9 link	c.1421C>T	p.Ala474Val	missense_variant	Exon 9 of 13	1	NM_005104.4	ENSP00000363958.4		P25440-1

Frequencies

GnomAD3 genomes

AF:

0.0237

AC:

3597

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00647

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0244

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.0247

Gnomad SAS

AF:

0.0384

Gnomad FIN

AF:

0.0141

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0351

Gnomad OTH

AF:

0.0272

GnomAD2 exomes

AF:

0.0293

AC:

7213

AN:

246574

AF XY:

0.0305

show subpopulations

Gnomad AFR exome

AF:

0.00662

Gnomad AMR exome

AF:

0.0251

Gnomad ASJ exome

AF:

0.0130

Gnomad EAS exome

AF:

0.0240

Gnomad FIN exome

AF:

0.0135

Gnomad NFE exome

AF:

0.0348

Gnomad OTH exome

AF:

0.0344

GnomAD4 exome

AF:

0.0315

AC:

46009

AN:

1460806

Hom.:

796

Cov.:

AF XY:

0.0321

AC XY:

23328

AN XY:

726720

show subpopulations

African (AFR)

AF:

0.00484

AC:

162

AN:

33480

American (AMR)

AF:

0.0255

AC:

1139

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0131

AC:

343

AN:

26136

East Asian (EAS)

AF:

0.0161

AC:

641

AN:

39700

South Asian (SAS)

AF:

0.0447

AC:

3853

AN:

86258

European-Finnish (FIN)

AF:

0.0151

AC:

791

AN:

52348

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0335

AC:

37305

AN:

1112006

Other (OTH)

AF:

0.0284

AC:

1714

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

2850

5700

8551

11401

14251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1386

2772

4158

5544

6930

<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:

0.0236

AC:

3597

AN:

152196

Hom.:

Cov.:

AF XY:

0.0231

AC XY:

1720

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00645

AC:

268

AN:

41528

American (AMR)

AF:

0.0243

AC:

372

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

AN:

3466

East Asian (EAS)

AF:

0.0245

AC:

127

AN:

5174

South Asian (SAS)

AF:

0.0388

AC:

187

AN:

4818

European-Finnish (FIN)

AF:

0.0141

AC:

149

AN:

10602

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0351

AC:

2385

AN:

67992

Other (OTH)

AF:

0.0269

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

179

359

538

718

897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0311

Hom.:

342

Bravo

AF:

0.0233

TwinsUK

AF:

0.0345

AC:

128

ALSPAC

AF:

0.0306

AC:

118

ESP6500AA

AF:

0.00860

AC:

ESP6500EA

AF:

0.0344

AC:

186

ExAC

AF:

0.0295

AC:

3493

Asia WGS

AF:

0.0480

AC:

169

AN:

3478

EpiCase

AF:

0.0328

EpiControl

AF:

0.0344

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BRD2-related disorder

Benign:1

May 08, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.070

T;T;.;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.49

.;.;T;.;.

MetaRNN

Benign

0.0034

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N;.;N;.

PhyloP100

1.5

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.28

N;N;.;N;N

REVEL

Benign

0.080

Sift

Benign

0.26

T;T;.;T;T

Sift4G

Benign

0.41

T;T;T;T;T

Polyphen

0.0020

B;B;.;.;.

Vest4

0.063

ClinPred

0.0021

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.057

gMVP

0.17

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over