3-114130718-C-T

Variant names:

• chr3-114130718-C-T
• rs4646996
• NM_000796.6:c.1006+400G>A

Variant summary

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

The NM_000796.6(DRD3):​c.1006+400G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,960 control chromosomes in the GnomAD database, including 15,385 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 0.44 (15385 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 16 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000796.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD3	NM_000796.6	MANE Select	c.1006+400G>A		intron	N/A	NP_000787.2	X5D2G4
	DRD3	NM_001282563.2		c.1006+400G>A		intron	N/A	NP_001269492.1	P35462-1
	DRD3	NM_001290809.1		c.1006+400G>A		intron	N/A	NP_001277738.1	X5D2G4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD3	ENST00000383673.5	TSL:1 MANE Select	c.1006+400G>A		intron	N/A	ENSP00000373169.2	P35462-1
	DRD3	ENST00000467632.5	TSL:1	c.1006+400G>A		intron	N/A	ENSP00000420662.1	P35462-1
	DRD3	ENST00000460779.5	TSL:2	c.1006+400G>A		intron	N/A	ENSP00000419402.1	P35462-1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66262 AN: 151842 Hom.: 15380 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.436 AC: 66271 AN: 151960 Hom.: 15385 Cov.: 32 AF XY: 0.439 AC XY: 32588 AN XY: 74282

African (AFR) AF: 0.265 AC: 10963 AN: 41434

American (AMR) AF: 0.522 AC: 7964 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2071 AN: 3472

East Asian (EAS) AF: 0.532 AC: 2754 AN: 5174

South Asian (SAS) AF: 0.492 AC: 2374 AN: 4822

European-Finnish (FIN) AF: 0.451 AC: 4749 AN: 10530

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.497 AC: 33746 AN: 67956

Other (OTH) AF: 0.479 AC: 1008 AN: 2106

Alfa AF: 0.458 Hom.: 6077

Bravo AF: 0.433

Asia WGS AF: 0.470 AC: 1633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.62
PhyloP100		-0.43
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: rs4646996; hg19: chr3-113849565;