rs2630349

Variant names:

• chr3-114154525-A-G
• rs2630349
• NM_000796.6:c.383+5230T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000796.6(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 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.383+5230T>C		intron_variant	Intron 3 of 6	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.383+5230T>C		intron_variant	Intron 4 of 7		NP_001269492.1
DRD3	NM_001290809.1	c.383+5230T>C		intron_variant	Intron 4 of 7		NP_001277738.1
DRD3	NM_033663.6	c.383+5230T>C		intron_variant	Intron 3 of 7		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.383+5230T>C		intron_variant	Intron 3 of 6	1	NM_000796.6	ENSP00000373169.2

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

African (AFR) AF: 0.681 AC: 28225 AN: 41456

American (AMR) AF: 0.896 AC: 13705 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.963 AC: 3343 AN: 3470

East Asian (EAS) AF: 0.885 AC: 4588 AN: 5184

South Asian (SAS) AF: 0.888 AC: 4272 AN: 4810

European-Finnish (FIN) AF: 0.955 AC: 10131 AN: 10608

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.940 AC: 63947 AN: 68030

Other (OTH) AF: 0.880 AC: 1858 AN: 2112

Alfa AF: 0.921 Hom.: 104511

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
PhyloP100		1.7
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: rs2630349; hg19: chr3-113873372;