3-114162166-C-T

Variant names:

• chr3-114162166-C-T
• rs226082
• NM_000796.6:c.271-2299G>A

Variant summary

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

The NM_000796.6(DRD3):​c.271-2299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,044 control chromosomes in the GnomAD database, including 29,214 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 0.60 (29214 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.271-2299G>A		intron_variant	Intron 2 of 6	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.271-2299G>A		intron_variant	Intron 3 of 7		NP_001269492.1
DRD3	NM_001290809.1	c.271-2299G>A		intron_variant	Intron 3 of 7		NP_001277738.1
DRD3	NM_033663.6	c.271-2299G>A		intron_variant	Intron 2 of 7		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.271-2299G>A		intron_variant	Intron 2 of 6	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90722 AN: 151926 Hom.: 29211 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.597 AC: 90761 AN: 152044 Hom.: 29214 Cov.: 32 AF XY: 0.596 AC XY: 44287 AN XY: 74332

African (AFR) AF: 0.343 AC: 14238 AN: 41450

American (AMR) AF: 0.567 AC: 8658 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2484 AN: 3472

East Asian (EAS) AF: 0.723 AC: 3735 AN: 5164

South Asian (SAS) AF: 0.662 AC: 3195 AN: 4826

European-Finnish (FIN) AF: 0.695 AC: 7357 AN: 10584

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.720 AC: 48934 AN: 67974

Other (OTH) AF: 0.618 AC: 1306 AN: 2114

Alfa AF: 0.681 Hom.: 20141

Bravo AF: 0.577

Asia WGS AF: 0.666 AC: 2315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.0
DANN	Benign	0.60
PhyloP100		-0.063
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: rs226082; hg19: chr3-113881013;