19-15284812-T-G

Variant names:

• chr19-15284812-T-G
• rs4808278
• NM_001379291.1:c.-34-11679A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001379291.1(BRD4):​c.-34-11679A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: BRD4 NM_001379291.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD4	NM_001379291.1	MANE Select	c.-34-11679A>C		intron	N/A	NP_001366220.1
	BRD4	NM_001330384.2		c.-34-11679A>C		intron	N/A	NP_001317313.1
	BRD4	NM_001379292.1		c.-34-11679A>C		intron	N/A	NP_001366221.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD4	ENST00000679869.1	MANE Select	c.-34-11679A>C		intron	N/A	ENSP00000506350.1
	BRD4	ENST00000360016.9	TSL:1	c.-34-11679A>C		intron	N/A	ENSP00000353112.4
	BRD4	ENST00000594841.5	TSL:1	c.-34-11679A>C		intron	N/A	ENSP00000470481.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.1
DANN	Benign	0.45
PhyloP100		0.52

Splicing

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

Other links and lift over

dbSNP: rs4808278; hg19: chr19-15395623;