rs12518222

Positions:

• chr5-175440166-C-T

Variant summary

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

The NM_000794.5(DRD1):​c.*1593G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 151,832 control chromosomes in the GnomAD database, including 1,395 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 0.13 (1395 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DRD1 NM_000794.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

Genes affected

DRD1 (HGNC:3020): (dopamine receptor D1) This gene encodes the D1 subtype of the dopamine receptor. The D1 subtype is the most abundant dopamine receptor in the central nervous system. This G-protein coupled receptor stimulates adenylyl cyclase and activates cyclic AMP-dependent protein kinases. D1 receptors regulate neuronal growth and development, mediate some behavioral responses, and modulate dopamine receptor D2-mediated events. Alternate transcription initiation sites result in two transcript variants of this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD1	NM_000794.5	c.*1593G>A		3_prime_UTR_variant	2/2	ENST00000393752.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD1	ENST00000393752.3	c.*1593G>A		3_prime_UTR_variant	2/2	2	NM_000794.5	P1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20053 AN: 151714 Hom.: 1390 Cov.: 32

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.138

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.132 AC: 20056 AN: 151832 Hom.: 1395 Cov.: 32 AF XY: 0.133 AC XY: 9841 AN XY: 74144

Gnomad4 AFR AF: 0.0877

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.144

Alfa AF: 0.130 Hom.: 238

Bravo AF: 0.128

Asia WGS AF: 0.220 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.72

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: rs12518222; hg19: chr5-174867169;