5-175439917-T-C

Variant names:

• chr5-175439917-T-C
• rs251937
• NM_000794.5:c.*1842A>G

Variant summary

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

The NM_000794.5(DRD1):​c.*1842A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,964 control chromosomes in the GnomAD database, including 7,394 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 0.31 (7394 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DRD1 NM_000794.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD1	NM_000794.5	c.*1842A>G		downstream_gene_variant		ENST00000393752.3	NP_000785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD1	ENST00000393752.3	c.*1842A>G		downstream_gene_variant		2	NM_000794.5	ENSP00000377353.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46639 AN: 151846 Hom.: 7382 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.307 AC: 46681 AN: 151964 Hom.: 7394 Cov.: 32 AF XY: 0.310 AC XY: 23000 AN XY: 74276

African (AFR) AF: 0.250 AC: 10382 AN: 41460

American (AMR) AF: 0.378 AC: 5775 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1032 AN: 3466

East Asian (EAS) AF: 0.425 AC: 2196 AN: 5172

South Asian (SAS) AF: 0.292 AC: 1405 AN: 4812

European-Finnish (FIN) AF: 0.293 AC: 3082 AN: 10526

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.321 AC: 21785 AN: 67946

Other (OTH) AF: 0.321 AC: 678 AN: 2114

Alfa AF: 0.314 Hom.: 6500

Bravo AF: 0.309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.78
PhyloP100		0.17

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs251937; hg19: chr5-174866920;