Variant 5-138164976-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_139199.2(BRD8):c.1469C>T(p.Thr490Met) variant causes a missense change. The variant allele was found at a frequency of 0.169 in 1,613,960 control chromosomes in the GnomAD database, including 24,967 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.

Frequency

Genomes: 𝑓 0.13 ( 1641 hom., cov: 32)

Exomes 𝑓: 0.17 ( 23326 hom. )

Consequence

BRD8
NM_139199.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.98

Variant links:

Genes affected

BRD8 (HGNC:19874): (bromodomain containing 8) The protein encoded by this gene interacts with thyroid hormone receptor in a ligand-dependent manner and enhances thyroid hormone-dependent activation from thyroid response elements. This protein contains a bromodomain and is thought to be a nuclear receptor coactivator. Multiple alternatively spliced transcript variants that encode distinct isoforms have been identified. [provided by RefSeq, Jul 2014]

BRD8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015330613).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD8	NM_139199.2 linkuse as main transcript	c.1469C>T	p.Thr490Met	missense_variant	12/27	ENST00000254900.10	NP_631938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRD8	ENST00000254900.10 linkuse as main transcript	c.1469C>T	p.Thr490Met	missense_variant	12/27	1	NM_139199.2	ENSP00000254900	P1	Q9H0E9-1

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20362

AN:

151960

Hom.:

1643

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0726

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.0913

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.0119

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.122

GnomAD3 exomes

AF:

0.148

AC:

37120

AN:

251362

Hom.:

3223

AF XY:

0.154

AC XY:

20917

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0733

Gnomad AMR exome

AF:

0.0852

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.0113

Gnomad SAS exome

AF:

0.214

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.179

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.172

AC:

252118

AN:

1461882

Hom.:

23326

Cov.:

AF XY:

0.174

AC XY:

126464

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0686

Gnomad4 AMR exome

AF:

0.0873

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.0107

Gnomad4 SAS exome

AF:

0.216

Gnomad4 FIN exome

AF:

0.183

Gnomad4 NFE exome

AF:

0.184

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.134

AC:

20357

AN:

152078

Hom.:

1641

Cov.:

AF XY:

0.133

AC XY:

9916

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0725

Gnomad4 AMR

AF:

0.0911

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.0122

Gnomad4 SAS

AF:

0.218

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.180

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.161

Hom.:

5343

Bravo

AF:

0.122

TwinsUK

AF:

0.184

AC:

683

ALSPAC

AF:

0.181

AC:

699

ESP6500AA

AF:

0.0824

AC:

363

ESP6500EA

AF:

0.174

AC:

1496

ExAC

AF:

0.152

AC:

18453

Asia WGS

AF:

0.130

AC:

453

AN:

3478

EpiCase

AF:

0.164

EpiControl

AF:

0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;.;T;.;.;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.76

T;T;T;T;T;T

MetaRNN

Benign

0.0015

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.;.;.;.

MutationTaster

Benign

0.0086

P;P;P;P;P

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.2

N;N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.037

D;D;D;D;D;D

Sift4G

Uncertain

0.046

D;D;T;T;D;T

Polyphen

0.99

D;.;.;D;.;D

Vest4

0.11

MPC

0.41

ClinPred

0.028

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.052

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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