rs1486009

Variant names:

• chr3-114169685-A-G
• rs1486009
• NM_000796.6:c.270+2038T>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+2038T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 152,090 control chromosomes in the GnomAD database, including 372 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 0.066 (372 hom., cov: 30)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914
• Publications: 15 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.098 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.270+2038T>C		intron_variant	Intron 2 of 6	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.270+2038T>C		intron_variant	Intron 3 of 7		NP_001269492.1
DRD3	NM_001290809.1	c.270+2038T>C		intron_variant	Intron 3 of 7		NP_001277738.1
DRD3	NM_033663.6	c.270+2038T>C		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.270+2038T>C		intron_variant	Intron 2 of 6	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 10029 AN: 151972 Hom.: 372 Cov.: 30

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0847

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.0103

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0576

Gnomad OTH AF: 0.0765

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

GnomAD4 genome AF: 0.0660 AC: 10037 AN: 152090 Hom.: 372 Cov.: 30 AF XY: 0.0689 AC XY: 5124 AN XY: 74332

African (AFR) AF: 0.0620 AC: 2574 AN: 41500

American (AMR) AF: 0.0850 AC: 1299 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0677 AC: 235 AN: 3470

East Asian (EAS) AF: 0.0103 AC: 53 AN: 5156

South Asian (SAS) AF: 0.106 AC: 508 AN: 4810

European-Finnish (FIN) AF: 0.119 AC: 1258 AN: 10572

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0576 AC: 3915 AN: 67984

Other (OTH) AF: 0.0766 AC: 162 AN: 2114

Alfa AF: 0.0602 Hom.: 930

Bravo AF: 0.0621

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.27
DANN	Benign	0.40
PhyloP100		-0.91
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: rs1486009; hg19: chr3-113888532;