rs16980448

Positions:

• chr19-15273887-C-A
• chr19-15273887-C-T

Variant summary

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

The NM_001379291.1(BRD4):​c.-34-754G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0375 in 146,190 control chromosomes in the GnomAD database, including 276 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 0.037 (276 hom., cov: 31)
• Consequence: BRD4 NM_001379291.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRD4	NM_001379291.1	c.-34-754G>T		intron_variant		ENST00000679869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD4	ENST00000679869.1	c.-34-754G>T		intron_variant			NM_001379291.1	P1

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5465 AN: 146098 Hom.: 275 Cov.: 31

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0193

Gnomad ASJ AF: 0.00581

Gnomad EAS AF: 0.000410

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00667

Gnomad NFE AF: 0.00562

Gnomad OTH AF: 0.0251

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

GnomAD4 genome AF: 0.0375 AC: 5477 AN: 146190 Hom.: 276 Cov.: 31 AF XY: 0.0364 AC XY: 2568 AN XY: 70646

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0192

Gnomad4 ASJ AF: 0.00581

Gnomad4 EAS AF: 0.000411

Gnomad4 SAS AF: 0.0208

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00561

Gnomad4 OTH AF: 0.0249

Alfa AF: 0.00948 Hom.: 55

Bravo AF: 0.0409

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs16980448; hg19: chr19-15384698;