5-175441837-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000794.5(DRD1):c.1263A>G(p.Ser421=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 1,613,876 control chromosomes in the GnomAD database, including 780,558 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 0.99 (74282 hom., cov: 30)
  • Exomes 𝑓: 0.98 (706276 hom.)
• Consequence: DRD1 NM_000794.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-0.549 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD1	NM_000794.5	c.1263A>G	p.Ser421=	synonymous_variant	2/2	ENST00000393752.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD1	ENST00000393752.3	c.1263A>G	p.Ser421=	synonymous_variant	2/2	2	NM_000794.5	P1

Frequencies

GnomAD3 genomes AF: 0.988 AC: 150268 AN: 152120 Hom.: 74223 Cov.: 30

Gnomad AFR AF: 0.996

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.987

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.986

GnomAD3 exomes AF: 0.988 AC: 248229 AN: 251294 Hom.: 122611 AF XY: 0.987 AC XY: 134097 AN XY: 135802

Gnomad AFR exome AF: 0.996

Gnomad AMR exome AF: 0.992

Gnomad ASJ exome AF: 0.992

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.996

Gnomad FIN exome AF: 0.993

Gnomad NFE exome AF: 0.980

Gnomad OTH exome AF: 0.988

GnomAD4 exome AF: 0.983 AC: 1436852 AN: 1461638 Hom.: 706276 Cov.: 72 AF XY: 0.983 AC XY: 715031 AN XY: 727068

Gnomad4 AFR exome AF: 0.997

Gnomad4 AMR exome AF: 0.991

Gnomad4 ASJ exome AF: 0.993

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.995

Gnomad4 FIN exome AF: 0.992

Gnomad4 NFE exome AF: 0.980

Gnomad4 OTH exome AF: 0.985

GnomAD4 genome AF: 0.988 AC: 150386 AN: 152238 Hom.: 74282 Cov.: 30 AF XY: 0.988 AC XY: 73528 AN XY: 74430

Gnomad4 AFR AF: 0.996

Gnomad4 AMR AF: 0.987

Gnomad4 ASJ AF: 0.992

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.996

Gnomad4 FIN AF: 0.994

Gnomad4 NFE AF: 0.981

Gnomad4 OTH AF: 0.986

Alfa AF: 0.984 Hom.: 37976

Bravo AF: 0.987

Asia WGS AF: 0.998 AC: 3470 AN: 3478

EpiCase AF: 0.981

EpiControl AF: 0.978

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.74
Dann	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs155417; hg19: chr5-174868840;