rs11883009

Variant names:

• chr19-15284584-C-G
• rs11883009
• NM_001379291.1:c.-34-11451G>C

Variant summary

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

The NM_001379291.1(BRD4):​c.-34-11451G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 152,282 control chromosomes in the GnomAD database, including 115 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 0.025 (115 hom., cov: 32)
• Consequence: BRD4 NM_001379291.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD4	NM_001379291.1	c.-34-11451G>C		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.-34-11451G>C		intron_variant	Intron 1 of 19		NM_001379291.1	ENSP00000506350.1

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3766 AN: 152164 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00542

Gnomad OTH AF: 0.0187

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

GnomAD4 genome AF: 0.0248 AC: 3774 AN: 152282 Hom.: 115 Cov.: 32 AF XY: 0.0238 AC XY: 1769 AN XY: 74456

African (AFR) AF: 0.0700 AC: 2909 AN: 41544

American (AMR) AF: 0.0139 AC: 213 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0205 AC: 99 AN: 4826

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00541 AC: 368 AN: 68016

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.0149 Hom.: 5

Bravo AF: 0.0271

Asia WGS AF: 0.0110 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.43
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11883009; hg19: chr19-15395395;