rs4809130

Variant names:

• chr19-15277117-C-T
• rs4809130
• NM_001379291.1:c.-34-3984G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379291.1(BRD4):​c.-34-3984G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 152,244 control chromosomes in the GnomAD database, including 503 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.

• Frequency: Genomes: 𝑓 0.070 (503 hom., cov: 32)
• Consequence: BRD4 NM_001379291.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 9 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD4	NM_001379291.1	c.-34-3984G>A		intron_variant	Intron 1 of 19	ENST00000679869.1	NP_001366220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD4	ENST00000679869.1	c.-34-3984G>A		intron_variant	Intron 1 of 19		NM_001379291.1	ENSP00000506350.1

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 10635 AN: 152126 Hom.: 505 Cov.: 32

Gnomad AFR AF: 0.0192

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0799

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0698 AC: 10626 AN: 152244 Hom.: 503 Cov.: 32 AF XY: 0.0659 AC XY: 4906 AN XY: 74436

African (AFR) AF: 0.0191 AC: 793 AN: 41562

American (AMR) AF: 0.0567 AC: 868 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0888 AC: 308 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5184

South Asian (SAS) AF: 0.0149 AC: 72 AN: 4824

European-Finnish (FIN) AF: 0.0762 AC: 807 AN: 10586

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7488 AN: 68000

Other (OTH) AF: 0.0786 AC: 166 AN: 2112

Alfa AF: 0.0965 Hom.: 1164

Bravo AF: 0.0667

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.2
DANN	Benign	0.83
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4809130; hg19: chr19-15387928;