rs7625282

Positions:

• chr3-114162680-A-G

Variant summary

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

The NM_000796.6(DRD3):​c.271-2813T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,076 control chromosomes in the GnomAD database, including 5,840 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 0.27 (5840 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD3	NM_000796.6	c.271-2813T>C		intron_variant		ENST00000383673.5
DRD3	NM_001282563.2	c.271-2813T>C		intron_variant
DRD3	NM_001290809.1	c.271-2813T>C		intron_variant
DRD3	NM_033663.6	c.271-2813T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD3	ENST00000383673.5	c.271-2813T>C		intron_variant		1	NM_000796.6	P1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41389 AN: 151958 Hom.: 5835 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.272 AC: 41425 AN: 152076 Hom.: 5840 Cov.: 32 AF XY: 0.277 AC XY: 20552 AN XY: 74318

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.293

Alfa AF: 0.248 Hom.: 637

Bravo AF: 0.279

Asia WGS AF: 0.290 AC: 1007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
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: rs7625282; hg19: chr3-113881527;