rs324032

chr3-114158981-G-Achr3-114158981-G-C

Variant summary

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

The NM_000796.6(DRD3):c.383+774C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 151,820 control chromosomes in the GnomAD database, including 58,698 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 0.87 (58698 hom., cov: 28)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD3	NM_000796.6	c.383+774C>T		intron_variant		ENST00000383673.5
DRD3	NM_001282563.2	c.383+774C>T		intron_variant
DRD3	NM_001290809.1	c.383+774C>T		intron_variant
DRD3	NM_033663.6	c.383+774C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD3	ENST00000383673.5	c.383+774C>T		intron_variant		1	NM_000796.6	P1

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132572 AN: 151702 Hom.: 58690 Cov.: 28

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.929

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.874 AC: 132621 AN: 151820 Hom.: 58698 Cov.: 28 AF XY: 0.875 AC XY: 64948 AN XY: 74188

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.969

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.930

Gnomad4 FIN AF: 0.955

Gnomad4 NFE AF: 0.940

Gnomad4 OTH AF: 0.888

Alfa AF: 0.901 Hom.: 7739

Bravo AF: 0.862

Asia WGS AF: 0.909 AC: 3161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.5
Dann	Benign	0.69

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: rs324032; hg19: chr3-113877828;