chr3-114182971-T-C

Position:

• chr3-114182971-T-C

Variant summary

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

The NM_001282563.2(DRD3):​c.-155-4195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,070 control chromosomes in the GnomAD database, including 16,854 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 0.44 (16854 hom., cov: 32)
• Consequence: DRD3 NM_001282563.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936

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 (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD3	NM_001282563.2	c.-155-4195A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD3	ENST00000460779.5	c.-155-4195A>G		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67517 AN: 151952 Hom.: 16825 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.445 AC: 67609 AN: 152070 Hom.: 16854 Cov.: 32 AF XY: 0.443 AC XY: 32941 AN XY: 74338

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.412

Alfa AF: 0.392 Hom.: 1654

Bravo AF: 0.466

Asia WGS AF: 0.360 AC: 1252 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	5.2
DANN	Benign	0.93

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: rs7629232; hg19: chr3-113901818;