Genetic Variant NM_001379291.1:c.3984C>T (chr19-15238779-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001379291.1(BRD4):c.3984C>T(p.Ala1328Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000316 in 1,580,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

BRD4
NM_001379291.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.562

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Cornelia de Lange syndrome 6
Inheritance: AD Classification: STRONG Submitted by: G2P
Cornelia de Lange syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
multiple congenital anomalies/dysmorphic syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

BRD4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 19-15238779-G-A is Benign according to our data. Variant chr19-15238779-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3652533.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.562 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379291.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD4	NM_001379291.1	MANE Select	c.3984C>T	p.Ala1328Ala	synonymous	Exon 19 of 20	NP_001366220.1	O60885-1
	BRD4	NM_058243.3		c.3984C>T	p.Ala1328Ala	synonymous	Exon 19 of 20	NP_490597.1	O60885-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD4	ENST00000679869.1	MANE Select	c.3984C>T	p.Ala1328Ala	synonymous	Exon 19 of 20	ENSP00000506350.1	O60885-1
	BRD4	ENST00000263377.6	TSL:1	c.3984C>T	p.Ala1328Ala	synonymous	Exon 19 of 20	ENSP00000263377.1	O60885-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000876

AC:

AN:

228434

AF XY:

0.00000800

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000981

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1428528

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

705762

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32600

American (AMR)

AF:

0.0000239

AC:

AN:

41762

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24802

East Asian (EAS)

AF:

0.00

AC:

AN:

39014

South Asian (SAS)

AF:

0.00

AC:

AN:

83654

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4668

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1091678

Other (OTH)

AF:

0.00

AC:

AN:

58618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.5

(source)

DANN

Benign

0.90

PhyloP100

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over