5-175443899-A-G

Variant names:

• chr5-175443899-A-G
• rs265981
• NM_000794.5:c.-684T>C

Variant summary

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

The NM_000794.5(DRD1):​c.-684T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,836 control chromosomes in the GnomAD database, including 41,974 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 0.73 (41770 hom., cov: 33)
  • Exomes 𝑓: 0.77 (204 hom.)
• Consequence: DRD1 NM_000794.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• Publications: 49 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD1	NM_000794.5	c.-684T>C		5_prime_UTR_variant	Exon 1 of 2	ENST00000393752.3	NP_000785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD1	ENST00000393752.3	c.-684T>C		5_prime_UTR_variant	Exon 1 of 2	2	NM_000794.5	ENSP00000377353.1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110577 AN: 152052 Hom.: 41704 Cov.: 33

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.731

GnomAD4 exome AF: 0.772 AC: 514 AN: 666 Hom.: 204 Cov.: 0 AF XY: 0.765 AC XY: 413 AN XY: 540

African (AFR) AF: 1.00 AC: 18 AN: 18

American (AMR) AF: 0.875 AC: 7 AN: 8

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AF: 0.938 AC: 30 AN: 32

South Asian (SAS) AF: 0.625 AC: 5 AN: 8

European-Finnish (FIN) AF: 0.625 AC: 5 AN: 8

Middle Eastern (MID) AF: 1.00 AC: 4 AN: 4

European-Non Finnish (NFE) AF: 0.752 AC: 415 AN: 552

Other (OTH) AF: 0.813 AC: 26 AN: 32

GnomAD4 genome AF: 0.728 AC: 110708 AN: 152170 Hom.: 41770 Cov.: 33 AF XY: 0.727 AC XY: 54077 AN XY: 74396

African (AFR) AF: 0.930 AC: 38672 AN: 41572

American (AMR) AF: 0.742 AC: 11353 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2374 AN: 3468

East Asian (EAS) AF: 0.859 AC: 4415 AN: 5140

South Asian (SAS) AF: 0.594 AC: 2864 AN: 4818

European-Finnish (FIN) AF: 0.625 AC: 6608 AN: 10566

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.620 AC: 42178 AN: 67990

Other (OTH) AF: 0.733 AC: 1548 AN: 2112

Alfa AF: 0.671 Hom.: 97352

Bravo AF: 0.750

Asia WGS AF: 0.729 AC: 2533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.2
DANN	Benign	0.58
PhyloP100		0.099
PromoterAI		0.070	Neutral
Mutation Taster		=300/0	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: rs265981; hg19: chr5-174870902;