Variant rs3918144 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_005104.4(BRD2):c.146C>G(p.Ala49Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0155 in 1,614,232 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A49S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.012 ( 18 hom., cov: 32)

Exomes 𝑓: 0.016 ( 252 hom. )

Consequence

BRD2
NM_005104.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.61

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046857).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0124 (1895/152348) while in subpopulation SAS AF= 0.029 (140/4824). AF 95% confidence interval is 0.0251. There are 18 homozygotes in gnomad4. There are 951 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRD2	NM_005104.4 linkuse as main transcript	c.146C>G	p.Ala49Gly	missense_variant	3/13	ENST00000374825.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD2	ENST00000374825.9 linkuse as main transcript	c.146C>G	p.Ala49Gly	missense_variant	3/13	1	NM_005104.4	P2	P25440-1

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1897

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00287

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0292

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0177

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.0170

AC:

4282

AN:

251466

Hom.:

AF XY:

0.0188

AC XY:

2556

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00969

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.00114

Gnomad SAS exome

AF:

0.0362

Gnomad FIN exome

AF:

0.0193

Gnomad NFE exome

AF:

0.0187

Gnomad OTH exome

AF:

0.0218

GnomAD4 exome

AF:

0.0159

AC:

23188

AN:

1461884

Hom.:

252

Cov.:

AF XY:

0.0165

AC XY:

12022

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00230

Gnomad4 AMR exome

AF:

0.0103

Gnomad4 ASJ exome

AF:

0.00968

Gnomad4 EAS exome

AF:

0.000907

Gnomad4 SAS exome

AF:

0.0359

Gnomad4 FIN exome

AF:

0.0192

Gnomad4 NFE exome

AF:

0.0154

Gnomad4 OTH exome

AF:

0.0153

GnomAD4 genome

AF:

0.0124

AC:

1895

AN:

152348

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

951

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00286

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00231

Gnomad4 SAS

AF:

0.0290

Gnomad4 FIN

AF:

0.0153

Gnomad4 NFE

AF:

0.0177

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0163

Hom.:

Bravo

AF:

0.0117

ExAC

AF:

0.0180

AC:

2189

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0204

EpiControl

AF:

0.0194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.46

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T;.;.;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

.;.;D;.;.

MetaRNN

Benign

0.0047

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

L;L;.;L;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.1

N;N;.;N;N

REVEL

Benign

0.13

Sift

Benign

0.039

D;D;.;D;D

Sift4G

Benign

0.21

T;T;T;T;D

Polyphen

0.78

P;P;.;.;.

Vest4

0.50

ClinPred

0.019

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.15

gMVP

0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over