rs7633291

Variant names:

• chr3-114168221-T-G
• rs7633291
• NM_000796.6:c.270+3502A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000796.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD3	NM_000796.6	MANE Select	c.270+3502A>C		intron	N/A	NP_000787.2
	DRD3	NM_001282563.2		c.270+3502A>C		intron	N/A	NP_001269492.1
	DRD3	NM_001290809.1		c.270+3502A>C		intron	N/A	NP_001277738.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD3	ENST00000383673.5	TSL:1 MANE Select	c.270+3502A>C		intron	N/A	ENSP00000373169.2
	DRD3	ENST00000467632.5	TSL:1	c.270+3502A>C		intron	N/A	ENSP00000420662.1
	DRD3	ENST00000460779.5	TSL:2	c.270+3502A>C		intron	N/A	ENSP00000419402.1

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

African (AFR) AF: 0.197 AC: 8160 AN: 41512

American (AMR) AF: 0.290 AC: 4428 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1379 AN: 5178

South Asian (SAS) AF: 0.187 AC: 903 AN: 4818

European-Finnish (FIN) AF: 0.165 AC: 1752 AN: 10606

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13227 AN: 67976

Other (OTH) AF: 0.212 AC: 448 AN: 2114

Alfa AF: 0.197 Hom.: 5620

Bravo AF: 0.216

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.93
DANN	Benign	0.75
PhyloP100		-0.63
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: rs7633291; hg19: chr3-113887068;