chr3-114172702-C-G

Variant names:

• chr3-114172702-C-G
• rs1800828
• NM_000796.6:c.-35-675G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.289 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.-35-675G>C		intron	N/A	NP_000787.2
	DRD3	NM_001282563.2		c.-35-675G>C		intron	N/A	NP_001269492.1
	DRD3	NM_001290809.1		c.-35-675G>C		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.-35-675G>C		intron	N/A	ENSP00000373169.2
	DRD3	ENST00000467632.5	TSL:1	c.-35-675G>C		intron	N/A	ENSP00000420662.1
	DRD3	ENST00000460779.5	TSL:2	c.-35-675G>C		intron	N/A	ENSP00000419402.1

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

African (AFR) AF: 0.136 AC: 5665 AN: 41514

American (AMR) AF: 0.296 AC: 4523 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 737 AN: 3468

East Asian (EAS) AF: 0.280 AC: 1451 AN: 5176

South Asian (SAS) AF: 0.214 AC: 1029 AN: 4816

European-Finnish (FIN) AF: 0.199 AC: 2105 AN: 10592

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16330 AN: 67972

Other (OTH) AF: 0.213 AC: 451 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		1.0
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: rs1800828; hg19: chr3-113891549;