rs7638876

chr3-114175453-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000796.6(DRD3):c.-36+3204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,942 control chromosomes in the GnomAD database, including 21,288 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 0.48 (21288 hom., cov: 31)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD3	NM_000796.6	c.-36+3204A>G		intron_variant		ENST00000383673.5
DRD3	NM_001282563.2	c.-36+3204A>G		intron_variant
DRD3	NM_001290809.1	c.-36+473A>G		intron_variant
DRD3	NM_033663.6	c.-36+3204A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD3	ENST00000383673.5	c.-36+3204A>G		intron_variant		1	NM_000796.6	P1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73541 AN: 151824 Hom.: 21233 Cov.: 31

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.485 AC: 73663 AN: 151942 Hom.: 21288 Cov.: 31 AF XY: 0.485 AC XY: 36055 AN XY: 74268

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.451

Alfa AF: 0.394 Hom.: 3959

Bravo AF: 0.508

Asia WGS AF: 0.426 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.68
Dann	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs7638876; hg19: chr3-113894300;