chr3-114167721-G-A

Variant names:

• chr3-114167721-G-A
• rs7619130
• NM_000796.6:c.270+4002C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.052 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD3	NM_000796.6	MANE Select	c.270+4002C>T		intron	N/A	NP_000787.2
	DRD3	NM_001282563.2		c.270+4002C>T		intron	N/A	NP_001269492.1
	DRD3	NM_001290809.1		c.270+4002C>T		intron	N/A	NP_001277738.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD3	ENST00000383673.5	TSL:1 MANE Select	c.270+4002C>T		intron	N/A	ENSP00000373169.2
	DRD3	ENST00000467632.5	TSL:1	c.270+4002C>T		intron	N/A	ENSP00000420662.1
	DRD3	ENST00000460779.5	TSL:2	c.270+4002C>T		intron	N/A	ENSP00000419402.1

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

African (AFR) AF: 0.0539 AC: 2238 AN: 41514

American (AMR) AF: 0.0175 AC: 268 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0448 AC: 216 AN: 4822

European-Finnish (FIN) AF: 0.0211 AC: 223 AN: 10586

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0267 AC: 1817 AN: 68028

Other (OTH) AF: 0.0246 AC: 52 AN: 2112

Alfa AF: 0.0148 Hom.: 3

Bravo AF: 0.0313

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.20
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism

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: rs7619130; hg19: chr3-113886568;