chr19-15273887-C-A

Variant names:

• chr19-15273887-C-A
• rs16980448
• NM_001379291.1:c.-34-754G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 = 0.112 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD4	NM_001379291.1	MANE Select	c.-34-754G>T		intron	N/A	NP_001366220.1
	BRD4	NM_058243.3		c.-34-754G>T		intron	N/A	NP_490597.1
	BRD4	NM_001330384.2		c.-34-754G>T		intron	N/A	NP_001317313.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD4	ENST00000679869.1	MANE Select	c.-34-754G>T		intron	N/A	ENSP00000506350.1
	BRD4	ENST00000263377.6	TSL:1	c.-34-754G>T		intron	N/A	ENSP00000263377.1
	BRD4	ENST00000360016.9	TSL:1	c.-34-754G>T		intron	N/A	ENSP00000353112.4

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

African (AFR) AF: 0.115 AC: 4533 AN: 39470

American (AMR) AF: 0.0192 AC: 274 AN: 14288

Ashkenazi Jewish (ASJ) AF: 0.00581 AC: 20 AN: 3444

East Asian (EAS) AF: 0.000411 AC: 2 AN: 4870

South Asian (SAS) AF: 0.0208 AC: 96 AN: 4616

European-Finnish (FIN) AF: 0.00132 AC: 12 AN: 9104

Middle Eastern (MID) AF: 0.00719 AC: 2 AN: 278

European-Non Finnish (NFE) AF: 0.00561 AC: 377 AN: 67210

Other (OTH) AF: 0.0249 AC: 50 AN: 2012

Alfa AF: 0.0171 Hom.: 277

Bravo AF: 0.0409

Asia WGS AF: 0.0150 AC: 52 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	2.0
DANN	Benign	0.57
PhyloP100		0.17
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: rs16980448; hg19: chr19-15384698;