chr19-15241561-G-A

Variant names:

• chr19-15241561-G-A
• rs4808272
• NM_001379291.1:c.3169+1339C>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.3169+1339C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,084 control chromosomes in the GnomAD database, including 24,113 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 0.56 (24113 hom., cov: 33)
• Consequence: BRD4 NM_001379291.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD4	NM_001379291.1	c.3169+1339C>T		intron_variant	Intron 14 of 19	ENST00000679869.1	NP_001366220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD4	ENST00000679869.1	c.3169+1339C>T		intron_variant	Intron 14 of 19		NM_001379291.1	ENSP00000506350.1
BRD4	ENST00000263377.6	c.3169+1339C>T		intron_variant	Intron 14 of 19	1		ENSP00000263377.1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85388 AN: 151966 Hom.: 24094 Cov.: 33

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.562 AC: 85441 AN: 152084 Hom.: 24113 Cov.: 33 AF XY: 0.558 AC XY: 41480 AN XY: 74348

African (AFR) AF: 0.605 AC: 25092 AN: 41492

American (AMR) AF: 0.582 AC: 8908 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2035 AN: 3468

East Asian (EAS) AF: 0.637 AC: 3282 AN: 5154

South Asian (SAS) AF: 0.552 AC: 2660 AN: 4822

European-Finnish (FIN) AF: 0.463 AC: 4891 AN: 10566

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36709 AN: 67970

Other (OTH) AF: 0.608 AC: 1285 AN: 2112

Alfa AF: 0.551 Hom.: 62534

Bravo AF: 0.577

Asia WGS AF: 0.617 AC: 2147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.37
DANN	Benign	0.62
PhyloP100		-0.82
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: rs4808272; hg19: chr19-15352372;