5-175443147-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -0.465

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 -14 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 id is 511081.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD1	NM_000794.5	c.-48G>A		5_prime_UTR_variant	2/2	ENST00000393752.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD1	ENST00000393752.3	c.-48G>A		5_prime_UTR_variant	2/2	2	NM_000794.5	P1

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

GnomAD3 exomes AF: 0.680 AC: 151971 AN: 223510 Hom.: 52755 AF XY: 0.669 AC XY: 80207 AN XY: 119888

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 SAS exome AF: 0.571

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

Gnomad4 AFR exome AF: 0.899

Gnomad4 AMR exome AF: 0.755

Gnomad4 ASJ exome AF: 0.690

Gnomad4 EAS exome AF: 0.874

Gnomad4 SAS exome AF: 0.575

Gnomad4 FIN exome AF: 0.623

Gnomad4 NFE exome AF: 0.617

Gnomad4 OTH exome AF: 0.658

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

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.723

Alfa AF: 0.651 Hom.: 50457

Bravo AF: 0.736

Asia WGS AF: 0.725 AC: 2520 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 09, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.81
Dann	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs4532; hg19: chr5-174870150; COSMIC: COSV67104360;