rs8104223

Variant names:

• chr19-15252666-A-G
• rs8104223
• NM_001379291.1:c.2158+1486T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-15252666-A-G
• chr19-15252666-A-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.2158+1486T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,216 control chromosomes in the GnomAD database, including 4,396 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 0.21 (4396 hom., cov: 32)
• Consequence: BRD4 NM_001379291.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD4	NM_001379291.1	MANE Select	c.2158+1486T>C		intron	N/A	NP_001366220.1	O60885-1
	BRD4	NM_058243.3		c.2158+1486T>C		intron	N/A	NP_490597.1	O60885-1
	BRD4	NM_001379292.1		c.2158+1486T>C		intron	N/A	NP_001366221.1	O60885-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD4	ENST00000679869.1	MANE Select	c.2158+1486T>C		intron	N/A	ENSP00000506350.1	O60885-1
	BRD4	ENST00000263377.6	TSL:1	c.2158+1486T>C		intron	N/A	ENSP00000263377.1	O60885-1
	BRD4	ENST00000371835.8	TSL:1	c.2158+1486T>C		intron	N/A	ENSP00000360901.3	O60885-2

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32602 AN: 152098 Hom.: 4396 Cov.: 32

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.214 AC: 32600 AN: 152216 Hom.: 4396 Cov.: 32 AF XY: 0.208 AC XY: 15459 AN XY: 74430

African (AFR) AF: 0.0786 AC: 3268 AN: 41562

American (AMR) AF: 0.214 AC: 3276 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3470

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5172

South Asian (SAS) AF: 0.162 AC: 781 AN: 4824

European-Finnish (FIN) AF: 0.246 AC: 2606 AN: 10600

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21037 AN: 67980

Other (OTH) AF: 0.255 AC: 537 AN: 2110

Alfa AF: 0.260 Hom.: 3410

Bravo AF: 0.207

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.8
DANN	Benign	0.76
PhyloP100		0.23
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: rs8104223; hg19: chr19-15363477;