rs752306

chr11-637622-C-T

Variant summary

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

The NM_000797.4(DRD4):c.285+33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0587 in 1,538,546 control chromosomes in the GnomAD database, including 3,141 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 0.050 (268 hom., cov: 33)
  • Exomes 𝑓: 0.060 (2873 hom.)
• Consequence: DRD4 NM_000797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880

Genes affected

DRD4 (HGNC:3025): (dopamine receptor D4) This gene encodes the D4 subtype of the dopamine receptor. The D4 subtype is a G-protein coupled receptor which inhibits adenylyl cyclase. It is a target for drugs which treat schizophrenia and Parkinson disease. Mutations in this gene have been associated with various behavioral phenotypes, including autonomic nervous system dysfunction, attention deficit/hyperactivity disorder, and the personality trait of novelty seeking. This gene contains a polymorphic number (2-10 copies) of tandem 48 nt repeats; the sequence shown contains four repeats. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD4	NM_000797.4	c.285+33C>T		intron_variant		ENST00000176183.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD4	ENST00000176183.6	c.285+33C>T		intron_variant		1	NM_000797.4	P1

Frequencies

GnomAD3 genomes AF: 0.0499 AC: 7597 AN: 152176 Hom.: 269 Cov.: 33

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.0574

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0564

Gnomad OTH AF: 0.0655

GnomAD3 exomes AF: 0.0636 AC: 9053 AN: 142406 Hom.: 418 AF XY: 0.0662 AC XY: 5051 AN XY: 76328

Gnomad AFR exome AF: 0.0198

Gnomad AMR exome AF: 0.0321

Gnomad ASJ exome AF: 0.0215

Gnomad EAS exome AF: 0.195

Gnomad SAS exome AF: 0.0820

Gnomad FIN exome AF: 0.0583

Gnomad NFE exome AF: 0.0574

Gnomad OTH exome AF: 0.0650

GnomAD4 exome AF: 0.0597 AC: 82742 AN: 1386250 Hom.: 2873 Cov.: 33 AF XY: 0.0603 AC XY: 41237 AN XY: 684214

Gnomad4 AFR exome AF: 0.0185

Gnomad4 AMR exome AF: 0.0342

Gnomad4 ASJ exome AF: 0.0224

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.0843

Gnomad4 FIN exome AF: 0.0603

Gnomad4 NFE exome AF: 0.0576

Gnomad4 OTH exome AF: 0.0682

GnomAD4 genome AF: 0.0499 AC: 7593 AN: 152296 Hom.: 268 Cov.: 33 AF XY: 0.0506 AC XY: 3768 AN XY: 74460

Gnomad4 AFR AF: 0.0215

Gnomad4 AMR AF: 0.0458

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.0878

Gnomad4 FIN AF: 0.0574

Gnomad4 NFE AF: 0.0564

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0549 Hom.: 274

Bravo AF: 0.0476

Asia WGS AF: 0.121 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.5
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs752306; hg19: chr11-637622; COSMIC: COSV51562514; COSMIC: COSV51562514;