chr3-114162680-A-G

Variant names:

• chr3-114162680-A-G
• rs7625282
• NM_000796.6:c.271-2813T>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.271-2813T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,076 control chromosomes in the GnomAD database, including 5,840 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 0.27 (5840 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.271-2813T>C		intron_variant	Intron 2 of 6	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.271-2813T>C		intron_variant	Intron 3 of 7		NP_001269492.1
DRD3	NM_001290809.1	c.271-2813T>C		intron_variant	Intron 3 of 7		NP_001277738.1
DRD3	NM_033663.6	c.271-2813T>C		intron_variant	Intron 2 of 7		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.271-2813T>C		intron_variant	Intron 2 of 6	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41389 AN: 151958 Hom.: 5835 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.272 AC: 41425 AN: 152076 Hom.: 5840 Cov.: 32 AF XY: 0.277 AC XY: 20552 AN XY: 74318

African (AFR) AF: 0.261 AC: 10832 AN: 41464

American (AMR) AF: 0.375 AC: 5735 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 943 AN: 3466

East Asian (EAS) AF: 0.277 AC: 1432 AN: 5174

South Asian (SAS) AF: 0.292 AC: 1405 AN: 4816

European-Finnish (FIN) AF: 0.284 AC: 2998 AN: 10570

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17154 AN: 67988

Other (OTH) AF: 0.293 AC: 618 AN: 2112

Alfa AF: 0.249 Hom.: 663

Bravo AF: 0.279

Asia WGS AF: 0.290 AC: 1007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.41
PhyloP100		0.067
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: rs7625282; hg19: chr3-113881527;