Variant 5-138152651-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_139199.2(BRD8):c.2687T>C(p.Leu896Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00433 in 1,614,166 control chromosomes in the GnomAD database, including 249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.022 ( 123 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 126 hom. )

Consequence

BRD8
NM_139199.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.82

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019735992).

BP6

Variant 5-138152651-A-G is Benign according to our data. Variant chr5-138152651-A-G is described in ClinVar as [Benign]. Clinvar id is 776065.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRD8	NM_139199.2 linkuse as main transcript	c.2687T>C	p.Leu896Pro	missense_variant	21/27	ENST00000254900.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD8	ENST00000254900.10 linkuse as main transcript	c.2687T>C	p.Leu896Pro	missense_variant	21/27	1	NM_139199.2	P1	Q9H0E9-1
BRD8	ENST00000427976.1 linkuse as main transcript	c.5T>C	p.Leu2Pro	missense_variant	1/6	3

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3385

AN:

152156

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0758

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00607

AC:

1526

AN:

251376

Hom.:

AF XY:

0.00453

AC XY:

616

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.0781

Gnomad AMR exome

AF:

0.00520

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000370

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00246

AC:

3591

AN:

1461892

Hom.:

126

Cov.:

AF XY:

0.00222

AC XY:

1611

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0782

Gnomad4 AMR exome

AF:

0.00608

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000217

Gnomad4 OTH exome

AF:

0.00661

GnomAD4 genome

AF:

0.0223

AC:

3398

AN:

152274

Hom.:

123

Cov.:

AF XY:

0.0219

AC XY:

1628

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0760

Gnomad4 AMR

AF:

0.0108

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00469

Hom.:

Bravo

AF:

0.0261

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0688

AC:

303

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00749

AC:

910

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.71

T;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.84

MVP

0.77

MPC

0.53

ClinPred

0.033

GERP RS

5.4

Varity_R

0.52

gMVP

0.68

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over