Variant 5-138145841-A-C 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.3316T>G(p.Leu1106Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00627 in 1,613,976 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 53 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 93 hom. )

Consequence

BRD8
NM_139199.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.730

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=0.0018951297).

BP6

Variant 5-138145841-A-C is Benign according to our data. Variant chr5-138145841-A-C is described in ClinVar as [Benign]. Clinvar id is 783395.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0546 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.3316T>G	p.Leu1106Val	missense_variant	24/27	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.3316T>G	p.Leu1106Val	missense_variant	24/27	1	NM_139199.2	ENSP00000254900	P1	Q9H0E9-1
BRD8	ENST00000427976.1 linkuse as main transcript	c.634T>G	p.Leu212Val	missense_variant	4/6	3		ENSP00000392646

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2677

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0513

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00792

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00442

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.00752

AC:

1891

AN:

251386

Hom.:

AF XY:

0.00660

AC XY:

897

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0521

Gnomad AMR exome

AF:

0.00373

Gnomad ASJ exome

AF:

0.0206

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00189

Gnomad FIN exome

AF:

0.000924

Gnomad NFE exome

AF:

0.00512

Gnomad OTH exome

AF:

0.00734

GnomAD4 exome

AF:

0.00509

AC:

7438

AN:

1461714

Hom.:

Cov.:

AF XY:

0.00503

AC XY:

3659

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.0567

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.0224

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00259

Gnomad4 FIN exome

AF:

0.000880

Gnomad4 NFE exome

AF:

0.00353

Gnomad4 OTH exome

AF:

0.00778

GnomAD4 genome

AF:

0.0176

AC:

2681

AN:

152262

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1235

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0512

Gnomad4 AMR

AF:

0.00791

Gnomad4 ASJ

AF:

0.0219

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00443

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00789

Hom.:

Bravo

AF:

0.0201

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.0513

AC:

226

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00846

AC:

1027

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00682

EpiControl

AF:

0.00741

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

0.084

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.012

Sift

Benign

0.086

T;T

Sift4G

Uncertain

0.055

T;T

Polyphen

0.44

B;.

Vest4

0.30

MVP

0.18

MPC

0.13

ClinPred

0.019

GERP RS

2.9

Varity_R

0.064

gMVP

0.15

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