3-114150007-A-C

Position:

• chr3-114150007-A-C

Variant summary

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

The NM_000796.6(DRD3):​c.384-2450T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,130 control chromosomes in the GnomAD database, including 36,350 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 0.65 (36350 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD3	NM_000796.6	c.384-2450T>G		intron_variant		ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.384-2450T>G		intron_variant			NP_001269492.1
DRD3	NM_001290809.1	c.384-2450T>G		intron_variant			NP_001277738.1
DRD3	NM_033663.6	c.384-2450T>G		intron_variant			NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.384-2450T>G		intron_variant		1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98635 AN: 152012 Hom.: 36353 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.648 AC: 98640 AN: 152130 Hom.: 36350 Cov.: 32 AF XY: 0.649 AC XY: 48232 AN XY: 74374

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.782

Gnomad4 EAS AF: 0.830

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.664

Alfa AF: 0.752 Hom.: 9174

Bravo AF: 0.628

Asia WGS AF: 0.699 AC: 2431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.1
DANN	Benign	0.80

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: rs324035; hg19: chr3-113868854;