3-114175453-T-C

Variant names:

• chr3-114175453-T-C
• rs7638876
• NM_000796.6:c.-36+3204A>G

Variant summary

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

The NM_000796.6(DRD3):​c.-36+3204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,942 control chromosomes in the GnomAD database, including 21,288 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 0.48 (21288 hom., cov: 31)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 10 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.-36+3204A>G		intron_variant	Intron 1 of 6	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.-36+3204A>G		intron_variant	Intron 2 of 7		NP_001269492.1
DRD3	NM_001290809.1	c.-36+473A>G		intron_variant	Intron 2 of 7		NP_001277738.1
DRD3	NM_033663.6	c.-36+3204A>G		intron_variant	Intron 1 of 7		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.-36+3204A>G		intron_variant	Intron 1 of 6	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73541 AN: 151824 Hom.: 21233 Cov.: 31

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.485 AC: 73663 AN: 151942 Hom.: 21288 Cov.: 31 AF XY: 0.485 AC XY: 36055 AN XY: 74268

African (AFR) AF: 0.813 AC: 33713 AN: 41454

American (AMR) AF: 0.481 AC: 7348 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1056 AN: 3462

East Asian (EAS) AF: 0.322 AC: 1659 AN: 5148

South Asian (SAS) AF: 0.455 AC: 2189 AN: 4816

European-Finnish (FIN) AF: 0.343 AC: 3618 AN: 10552

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22652 AN: 67938

Other (OTH) AF: 0.451 AC: 949 AN: 2104

Alfa AF: 0.396 Hom.: 6021

Bravo AF: 0.508

Asia WGS AF: 0.426 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.41
PhyloP100		-2.0
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: rs7638876; hg19: chr3-113894300;