chr5-175443193-C-T

Variant names:

• chr5-175443193-C-T
• rs5326
• NM_000794.5:c.-94G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000794.5(DRD1):​c.-94G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,509,146 control chromosomes in the GnomAD database, including 17,865 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 0.15 (1715 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16150 hom.)
• Consequence: DRD1 NM_000794.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215
• Publications: 81 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD1	NM_000794.5	c.-94G>A		5_prime_UTR_variant	Exon 2 of 2	ENST00000393752.3	NP_000785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD1	ENST00000393752.3	c.-94G>A		5_prime_UTR_variant	Exon 2 of 2	2	NM_000794.5	ENSP00000377353.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22683 AN: 151998 Hom.: 1711 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.152 AC: 206354 AN: 1357030 Hom.: 16150 Cov.: 24 AF XY: 0.152 AC XY: 101461 AN XY: 666890

African (AFR) AF: 0.149 AC: 4545 AN: 30476

American (AMR) AF: 0.128 AC: 4126 AN: 32340

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 2986 AN: 20394

East Asian (EAS) AF: 0.267 AC: 10387 AN: 38832

South Asian (SAS) AF: 0.149 AC: 10595 AN: 71088

European-Finnish (FIN) AF: 0.189 AC: 9381 AN: 49674

Middle Eastern (MID) AF: 0.159 AC: 816 AN: 5144

European-Non Finnish (NFE) AF: 0.147 AC: 154906 AN: 1053104

Other (OTH) AF: 0.154 AC: 8612 AN: 55978

GnomAD4 genome AF: 0.149 AC: 22688 AN: 152116 Hom.: 1715 Cov.: 32 AF XY: 0.148 AC XY: 10998 AN XY: 74334

African (AFR) AF: 0.147 AC: 6097 AN: 41500

American (AMR) AF: 0.118 AC: 1799 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 491 AN: 3472

East Asian (EAS) AF: 0.244 AC: 1257 AN: 5152

South Asian (SAS) AF: 0.152 AC: 732 AN: 4820

European-Finnish (FIN) AF: 0.180 AC: 1901 AN: 10582

Middle Eastern (MID) AF: 0.145 AC: 42 AN: 290

European-Non Finnish (NFE) AF: 0.146 AC: 9919 AN: 67984

Other (OTH) AF: 0.154 AC: 326 AN: 2112

Alfa AF: 0.148 Hom.: 5412

Bravo AF: 0.147

Asia WGS AF: 0.223 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.47
PhyloP100		0.21
Mutation Taster		=299/1	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: rs5326; hg19: chr5-174870196; COSMIC: COSV67104399;