5-175443147-C-T

Variant names:

• chr5-175443147-C-T
• rs4532
• NM_000794.5:c.-48G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000794.5(DRD1):​c.-48G>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 0.643 in 1,578,260 control chromosomes in the GnomAD database, including 331,832 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (40015 hom., cov: 31)
  • Exomes 𝑓: 0.64 (291817 hom.)
• Consequence: DRD1 NM_000794.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.465
• Publications: 213 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-175443147-C-T is Benign according to our data. Variant chr5-175443147-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 511081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000794.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD1	NM_000794.5	MANE Select	c.-48G>A		5_prime_UTR	Exon 2 of 2	NP_000785.1	P21728

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD1	ENST00000393752.3	TSL:2 MANE Select	c.-48G>A		5_prime_UTR	Exon 2 of 2	ENSP00000377353.1	P21728
	DRD1	ENST00000950668.1		c.-48G>A		5_prime_UTR	Exon 3 of 3	ENSP00000620727.1
	DRD1	ENST00000950669.1		c.-48G>A		5_prime_UTR	Exon 2 of 2	ENSP00000620728.1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108547 AN: 151892 Hom.: 39954 Cov.: 31

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.721

GnomAD2 exomes AF: 0.680 AC: 151971 AN: 223510 AF XY: 0.669

Gnomad AFR exome AF: 0.891

Gnomad AMR exome AF: 0.762

Gnomad ASJ exome AF: 0.687

Gnomad EAS exome AF: 0.858

Gnomad FIN exome AF: 0.622

Gnomad NFE exome AF: 0.629

Gnomad OTH exome AF: 0.656

GnomAD4 exome AF: 0.636 AC: 906735 AN: 1426250 Hom.: 291817 Cov.: 42 AF XY: 0.633 AC XY: 446641 AN XY: 705048

African (AFR) AF: 0.899 AC: 29315 AN: 32596

American (AMR) AF: 0.755 AC: 31221 AN: 41326

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 16138 AN: 23382

East Asian (EAS) AF: 0.874 AC: 34401 AN: 39368

South Asian (SAS) AF: 0.575 AC: 45801 AN: 79624

European-Finnish (FIN) AF: 0.623 AC: 32503 AN: 52142

Middle Eastern (MID) AF: 0.763 AC: 4242 AN: 5556

European-Non Finnish (NFE) AF: 0.617 AC: 674451 AN: 1093500

Other (OTH) AF: 0.658 AC: 38663 AN: 58756

GnomAD4 genome AF: 0.715 AC: 108672 AN: 152010 Hom.: 40015 Cov.: 31 AF XY: 0.714 AC XY: 53077 AN XY: 74296

African (AFR) AF: 0.889 AC: 36865 AN: 41484

American (AMR) AF: 0.736 AC: 11254 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2374 AN: 3470

East Asian (EAS) AF: 0.857 AC: 4417 AN: 5154

South Asian (SAS) AF: 0.591 AC: 2839 AN: 4804

European-Finnish (FIN) AF: 0.624 AC: 6602 AN: 10574

Middle Eastern (MID) AF: 0.779 AC: 226 AN: 290

European-Non Finnish (NFE) AF: 0.620 AC: 42101 AN: 67930

Other (OTH) AF: 0.723 AC: 1524 AN: 2108

Alfa AF: 0.661 Hom.: 111792

Bravo AF: 0.736

Asia WGS AF: 0.725 AC: 2520 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.81
DANN	Benign	0.59
PhyloP100		-0.47
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4532; hg19: chr5-174870150; COSMIC: COSV67104360;