19-15252241-G-T

Variant names:

• chr19-15252241-G-T
• rs11880801
• NM_001379291.1:c.2158+1911C>A

Variant summary

Our verdict is Benign. Variant got -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

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 = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD4	NM_001379291.1	c.2158+1911C>A		intron_variant	Intron 11 of 19	ENST00000679869.1	NP_001366220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD4	ENST00000679869.1	c.2158+1911C>A		intron_variant	Intron 11 of 19		NM_001379291.1	ENSP00000506350.1
BRD4	ENST00000263377.6	c.2158+1911C>A		intron_variant	Intron 11 of 19	1		ENSP00000263377.1
BRD4	ENST00000371835.8	c.2158+1911C>A		intron_variant	Intron 11 of 11	1		ENSP00000360901.3

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

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0612

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.192

Alfa AF: 0.150 Hom.: 653

Bravo AF: 0.189

Asia WGS AF: 0.131 AC: 457 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	0.24
DANN	Benign	0.72

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: rs11880801; hg19: chr19-15363052;