rs6787134

Variant names:

• chr3-114183902-T-G
• rs6787134
• NM_001282563.2:c.-155-5126A>C

Variant summary

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

The NM_001282563.2(DRD3):​c.-155-5126A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,084 control chromosomes in the GnomAD database, including 1,318 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 0.13 (1318 hom., cov: 32)
• Consequence: DRD3 NM_001282563.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 4 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=-0.54).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_001282563.2	c.-155-5126A>C		intron_variant	Intron 1 of 7		NP_001269492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000460779.5	c.-155-5126A>C		intron_variant	Intron 1 of 7	2		ENSP00000419402.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19219 AN: 151966 Hom.: 1319 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0555

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0830

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.126 AC: 19235 AN: 152084 Hom.: 1318 Cov.: 32 AF XY: 0.125 AC XY: 9307 AN XY: 74344

African (AFR) AF: 0.119 AC: 4944 AN: 41514

American (AMR) AF: 0.103 AC: 1567 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 498 AN: 3468

East Asian (EAS) AF: 0.0552 AC: 286 AN: 5180

South Asian (SAS) AF: 0.181 AC: 872 AN: 4822

European-Finnish (FIN) AF: 0.0830 AC: 878 AN: 10574

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9676 AN: 67930

Other (OTH) AF: 0.144 AC: 305 AN: 2114

Alfa AF: 0.140 Hom.: 2458

Bravo AF: 0.124

Asia WGS AF: 0.127 AC: 440 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.0
DANN	Benign	0.96
PhyloP100		0.21
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: rs6787134; hg19: chr3-113902749;