3-114172702-C-G

Position:

• chr3-114172702-C-G

Variant summary

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

The NM_000796.6(DRD3):​c.-35-675G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,144 control chromosomes in the GnomAD database, including 3,804 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 0.21 (3804 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.998

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD3	NM_000796.6	c.-35-675G>C		intron_variant		ENST00000383673.5
DRD3	NM_001282563.2	c.-35-675G>C		intron_variant
DRD3	NM_001290809.1	c.-35-675G>C		intron_variant
DRD3	NM_033663.6	c.-35-675G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD3	ENST00000383673.5	c.-35-675G>C		intron_variant		1	NM_000796.6	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32642 AN: 152026 Hom.: 3802 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.215 AC: 32651 AN: 152144 Hom.: 3804 Cov.: 32 AF XY: 0.216 AC XY: 16039 AN XY: 74390

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.213

Alfa AF: 0.211 Hom.: 466

Bravo AF: 0.220

Asia WGS AF: 0.237 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.84

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: rs1800828; hg19: chr3-113891549;