rs4808278

Positions:

• chr19-15284812-T-A
• chr19-15284812-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379291.1(BRD4):​c.-34-11679A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,298 control chromosomes in the GnomAD database, including 62,416 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 0.90 (62416 hom., cov: 32)
• Consequence: BRD4 NM_001379291.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRD4	NM_001379291.1	c.-34-11679A>T		intron_variant		ENST00000679869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD4	ENST00000679869.1	c.-34-11679A>T		intron_variant			NM_001379291.1	P1

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137436 AN: 152180 Hom.: 62363 Cov.: 32

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.916

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

GnomAD4 genome AF: 0.903 AC: 137541 AN: 152298 Hom.: 62416 Cov.: 32 AF XY: 0.899 AC XY: 66911 AN XY: 74460

Gnomad4 AFR AF: 0.978

Gnomad4 AMR AF: 0.848

Gnomad4 ASJ AF: 0.954

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.865

Gnomad4 NFE AF: 0.890

Gnomad4 OTH AF: 0.916

Alfa AF: 0.899 Hom.: 7642

Bravo AF: 0.904

Asia WGS AF: 0.812 AC: 2823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4808278; hg19: chr19-15395623;