5-175441837-T-C

Variant names:

• chr5-175441837-T-C
• rs155417
• NM_000794.5:c.1263A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000794.5(DRD1):​c.1263A>G​(p.Ser421Ser) 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
• Publications: 22 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 -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 rank	MANE	Protein	UniProt
DRD1	NM_000794.5	c.1263A>G	p.Ser421Ser	synonymous_variant	Exon 2 of 2	ENST00000393752.3	NP_000785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD1	ENST00000393752.3	c.1263A>G	p.Ser421Ser	synonymous_variant	Exon 2 of 2	2	NM_000794.5	ENSP00000377353.1

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

GnomAD2 exomes AF: 0.988 AC: 248229 AN: 251294 AF XY: 0.987

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 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

African (AFR) AF: 0.997 AC: 33374 AN: 33472

American (AMR) AF: 0.991 AC: 44320 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 25950 AN: 26130

East Asian (EAS) AF: 1.00 AC: 39692 AN: 39694

South Asian (SAS) AF: 0.995 AC: 85807 AN: 86206

European-Finnish (FIN) AF: 0.992 AC: 52980 AN: 53416

Middle Eastern (MID) AF: 0.990 AC: 5711 AN: 5768

European-Non Finnish (NFE) AF: 0.980 AC: 1089516 AN: 1111864

Other (OTH) AF: 0.985 AC: 59502 AN: 60386

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

African (AFR) AF: 0.996 AC: 41383 AN: 41536

American (AMR) AF: 0.987 AC: 15100 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3445 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5148 AN: 5148

South Asian (SAS) AF: 0.996 AC: 4803 AN: 4820

European-Finnish (FIN) AF: 0.994 AC: 10556 AN: 10618

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.981 AC: 66734 AN: 68030

Other (OTH) AF: 0.986 AC: 2083 AN: 2112

Alfa AF: 0.984 Hom.: 50394

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
PhyloP100		-0.55
Mutation Taster		=100/0	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: rs155417; hg19: chr5-174868840; COSMIC: COSV108234584;