rs7633291

chr3-114168221-T-G

Variant summary

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

The NM_000796.6(DRD3):c.270+3502A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,156 control chromosomes in the GnomAD database, including 3,360 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 (3360 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631

Genes affected

DRD3 (HGNC:3024): (dopamine receptor D3) This gene encodes the D3 subtype of the five (D1-D5) dopamine receptors. The activity of the D3 subtype receptor is mediated by G proteins which inhibit adenylyl cyclase. This receptor is localized to the limbic areas of the brain, which are associated with cognitive, emotional, and endocrine functions. Genetic variation in this gene may be associated with susceptibility to hereditary essential tremor 1. Alternative splicing of this gene results in transcript variants encoding different isoforms, although some variants may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD3	NM_000796.6	c.270+3502A>C		intron_variant		ENST00000383673.5
DRD3	NM_001282563.2	c.270+3502A>C		intron_variant
DRD3	NM_001290809.1	c.270+3502A>C		intron_variant
DRD3	NM_033663.6	c.270+3502A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD3	ENST00000383673.5	c.270+3502A>C		intron_variant		1	NM_000796.6	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31249 AN: 152038 Hom.: 3357 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.206 AC: 31274 AN: 152156 Hom.: 3360 Cov.: 32 AF XY: 0.207 AC XY: 15386 AN XY: 74380

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.212

Alfa AF: 0.195 Hom.: 1465

Bravo AF: 0.216

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.93
Dann	Benign	0.75

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: rs7633291; hg19: chr3-113887068;