19-15252241-G-T

Variant names:

• chr19-15252241-G-T
• rs11880801
• NM_001379291.1:c.2158+1911C>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.2158+1911C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,164 control chromosomes in the GnomAD database, including 2,979 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 0.19 (2979 hom., cov: 32)
• Consequence: BRD4 NM_001379291.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

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.2158+1911C>A		intron	N/A	NP_001366220.1	O60885-1
	BRD4	NM_058243.3		c.2158+1911C>A		intron	N/A	NP_490597.1	O60885-1
	BRD4	NM_001379292.1		c.2158+1911C>A		intron	N/A	NP_001366221.1	O60885-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD4	ENST00000679869.1	MANE Select	c.2158+1911C>A		intron	N/A	ENSP00000506350.1	O60885-1
	BRD4	ENST00000263377.6	TSL:1	c.2158+1911C>A		intron	N/A	ENSP00000263377.1	O60885-1
	BRD4	ENST00000371835.8	TSL:1	c.2158+1911C>A		intron	N/A	ENSP00000360901.3	O60885-2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29335 AN: 152046 Hom.: 2966 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0611

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.193 AC: 29387 AN: 152164 Hom.: 2979 Cov.: 32 AF XY: 0.193 AC XY: 14392 AN XY: 74408

African (AFR) AF: 0.244 AC: 10106 AN: 41486

American (AMR) AF: 0.151 AC: 2315 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 595 AN: 3468

East Asian (EAS) AF: 0.0612 AC: 317 AN: 5180

South Asian (SAS) AF: 0.196 AC: 947 AN: 4824

European-Finnish (FIN) AF: 0.197 AC: 2083 AN: 10598

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12285 AN: 67994

Other (OTH) AF: 0.192 AC: 406 AN: 2114

Alfa AF: 0.158 Hom.: 862

Bravo AF: 0.189

Asia WGS AF: 0.131 AC: 457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.72
PhyloP100		-0.96
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: rs11880801; hg19: chr19-15363052;