rs167771

Positions:

• chr3-114157428-G-A
• chr3-114157428-G-C
• chr3-114157428-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000796.6(DRD3):​c.383+2327C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 151,878 control chromosomes in the GnomAD database, including 36,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.65 (36887 hom., cov: 30)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.928

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-114157428-G-A is Benign according to our data. Variant chr3-114157428-G-A is described in ClinVar as [Benign]. Clinvar id is 512983.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD3	NM_000796.6	c.383+2327C>T		intron_variant		ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.383+2327C>T		intron_variant			NP_001269492.1
DRD3	NM_001290809.1	c.383+2327C>T		intron_variant			NP_001277738.1
DRD3	NM_033663.6	c.383+2327C>T		intron_variant			NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.383+2327C>T		intron_variant		1	NM_000796.6	ENSP00000373169	P1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98529 AN: 151760 Hom.: 36893 Cov.: 30

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.649 AC: 98528 AN: 151878 Hom.: 36887 Cov.: 30 AF XY: 0.648 AC XY: 48104 AN XY: 74218

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.807

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.667

Alfa AF: 0.803 Hom.: 110244

Bravo AF: 0.628

Asia WGS AF: 0.697 AC: 2427 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 09, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.093
DANN	Benign	0.66

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: rs167771; hg19: chr3-113876275;