rs2654754

Variant names:

• chr3-114136949-G-A
• rs2654754
• NM_000796.6:c.723+2551C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-114136949-G-A
• chr3-114136949-G-C
• chr3-114136949-G-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.723+2551C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 152,252 control chromosomes in the GnomAD database, including 61,402 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 0.89 (61402 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.723+2551C>T		intron_variant	Intron 5 of 6	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.723+2551C>T		intron_variant	Intron 6 of 7		NP_001269492.1
DRD3	NM_001290809.1	c.723+2551C>T		intron_variant	Intron 6 of 7		NP_001277738.1
DRD3	NM_033663.6	c.723+2551C>T		intron_variant	Intron 5 of 7		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.723+2551C>T		intron_variant	Intron 5 of 6	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135125 AN: 152134 Hom.: 61392 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.954

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.918

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

GnomAD4 genome AF: 0.888 AC: 135177 AN: 152252 Hom.: 61402 Cov.: 32 AF XY: 0.889 AC XY: 66189 AN XY: 74442

African (AFR) AF: 0.674 AC: 27973 AN: 41490

American (AMR) AF: 0.955 AC: 14603 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3434 AN: 3472

East Asian (EAS) AF: 0.989 AC: 5130 AN: 5188

South Asian (SAS) AF: 0.909 AC: 4391 AN: 4828

European-Finnish (FIN) AF: 0.979 AC: 10392 AN: 10614

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66149 AN: 68044

Other (OTH) AF: 0.918 AC: 1938 AN: 2112

Alfa AF: 0.948 Hom.: 113050

Bravo AF: 0.878

Asia WGS AF: 0.932 AC: 3242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.25
DANN	Benign	0.57
PhyloP100		-0.67
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: rs2654754; hg19: chr3-113855796;