19-15238785-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001379291.1(BRD4):c.3978G>T(p.Glu1326Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00082 in 1,584,550 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00080 ( 12 hom. )

Consequence

BRD4
NM_001379291.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.406

Variant links:

Genes affected

BRD4 (HGNC:13575): (bromodomain containing 4) The protein encoded by this gene is homologous to the murine protein MCAP, which associates with chromosomes during mitosis, and to the human RING3 protein, a serine/threonine kinase. Each of these proteins contains two bromodomains, a conserved sequence motif which may be involved in chromatin targeting. This gene has been implicated as the chromosome 19 target of translocation t(15;19)(q13;p13.1), which defines an upper respiratory tract carcinoma in young people. Two alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]

BRD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067904294).

BP6

Variant 19-15238785-C-A is Benign according to our data. Variant chr19-15238785-C-A is described in ClinVar as [Benign]. Clinvar id is 718290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00101 (154/152382) while in subpopulation AMR AF= 0.00882 (135/15314). AF 95% confidence interval is 0.00761. There are 2 homozygotes in gnomad4. There are 90 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 154 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD4	NM_001379291.1 link	c.3978G>T	p.Glu1326Asp	missense_variant	Exon 19 of 20	ENST00000679869.1	NP_001366220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD4	ENST00000679869.1 link	c.3978G>T	p.Glu1326Asp	missense_variant	Exon 19 of 20		NM_001379291.1	ENSP00000506350.1		O60885-1
BRD4	ENST00000263377.6 link	c.3978G>T	p.Glu1326Asp	missense_variant	Exon 19 of 20	1		ENSP00000263377.1		O60885-1

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

154

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00883

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00359

AC:

831

AN:

231328

Hom.:

AF XY:

0.00288

AC XY:

365

AN XY:

126724

show subpopulations

Gnomad AFR exome

AF:

0.000136

Gnomad AMR exome

AF:

0.0240

Gnomad ASJ exome

AF:

0.00225

Gnomad EAS exome

AF:

0.000451

Gnomad SAS exome

AF:

0.000453

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000969

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.000800

AC:

1146

AN:

1432168

Hom.:

Cov.:

AF XY:

0.000709

AC XY:

502

AN XY:

707918

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.0214

Gnomad4 ASJ exome

AF:

0.00135

Gnomad4 EAS exome

AF:

0.000615

Gnomad4 SAS exome

AF:

0.000451

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.000374

GnomAD4 genome

AF:

0.00101

AC:

154

AN:

152382

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00882

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000508

Hom.:

Bravo

AF:

0.00206

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00273

AC:

331

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

BRD4-related disorder

Benign:1

Jun 30, 2024

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

Uncertain

0.44

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.098

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0068

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.82

REVEL

Benign

0.15

Sift

Benign

0.078

Sift4G

Benign

0.096

Polyphen

0.99

Vest4

0.36

MutPred

0.17

Gain of MoRF binding (P = 0.0947);

MVP

0.37

MPC

1.1

ClinPred

0.055

GERP RS

-4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.095

gMVP

0.39

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