rs7619130

Positions:

• chr3-114167721-G-A
• chr3-114167721-G-C

Variant summary

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

The NM_000796.6(DRD3):​c.270+4002C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 152,214 control chromosomes in the GnomAD database, including 109 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 0.032 (109 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD3	NM_000796.6	c.270+4002C>T		intron_variant		ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.270+4002C>T		intron_variant			NP_001269492.1
DRD3	NM_001290809.1	c.270+4002C>T		intron_variant			NP_001277738.1
DRD3	NM_033663.6	c.270+4002C>T		intron_variant			NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.270+4002C>T		intron_variant		1	NM_000796.6	ENSP00000373169	P1

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4884 AN: 152096 Hom.: 110 Cov.: 32

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0452

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0267

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0321 AC: 4883 AN: 152214 Hom.: 109 Cov.: 32 AF XY: 0.0317 AC XY: 2362 AN XY: 74412

Gnomad4 AFR AF: 0.0539

Gnomad4 AMR AF: 0.0175

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0448

Gnomad4 FIN AF: 0.0211

Gnomad4 NFE AF: 0.0267

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0132 Hom.: 1

Bravo AF: 0.0313

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.20

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: rs7619130; hg19: chr3-113886568;