rs2630349

Positions:

• chr3-114154525-A-G
• chr3-114154525-A-T

Variant summary

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

The ENST00000383673.5(DRD3):​c.383+5230T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,170 control chromosomes in the GnomAD database, including 57,477 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 0.86 (57477 hom., cov: 31)
• Consequence: DRD3 ENST00000383673.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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=-0.48).
• 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	Protein	UniProt
DRD3	NM_000796.6	c.383+5230T>C		intron_variant		ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.383+5230T>C		intron_variant			NP_001269492.1
DRD3	NM_001290809.1	c.383+5230T>C		intron_variant			NP_001277738.1
DRD3	NM_033663.6	c.383+5230T>C		intron_variant			NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.383+5230T>C		intron_variant		1	NM_000796.6	ENSP00000373169	P1

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131066 AN: 152052 Hom.: 57468 Cov.: 31

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.883

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

GnomAD4 genome AF: 0.862 AC: 131113 AN: 152170 Hom.: 57477 Cov.: 31 AF XY: 0.863 AC XY: 64242 AN XY: 74408

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.896

Gnomad4 ASJ AF: 0.963

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.955

Gnomad4 NFE AF: 0.940

Gnomad4 OTH AF: 0.880

Alfa AF: 0.931 Hom.: 85513

Bravo AF: 0.848

Asia WGS AF: 0.878 AC: 3054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.86

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: rs2630349; hg19: chr3-113873372;