Genetic Variant DRD1:c.-684T>C (chr5-175443899-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0990

Publications

49 publications found

Variant links:

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]

DRD1 links:

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ACMG classification

Classification was made for transcript

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.

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.-684T>C		5_prime_UTR	Exon 1 of 2	NP_000785.1	P21728

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DRD1	ENST00000393752.3	TSL:2 MANE Select	c.-684T>C	5_prime_UTR	Exon 1 of 2	ENSP00000377353.1	P21728
DRD1	ENST00000950668.1		c.-684T>C	5_prime_UTR	Exon 2 of 3	ENSP00000620727.1
DRD1	ENST00000950669.1		c.-483-317T>C	intron	N/A	ENSP00000620728.1

Frequencies

GnomAD3 genomes

AF:

0.727

AC:

110577

AN:

152052

Hom.:

41704

Cov.:

show subpopulations

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.:

AF XY:

0.765

AC XY:

413

AN XY:

540

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.875

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.938

AC:

AN:

South Asian (SAS)

AF:

0.625

AC:

AN:

European-Finnish (FIN)

AF:

0.625

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.752

AC:

415

AN:

552

Other (OTH)

AF:

0.813

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.584

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.728

AC:

110708

AN:

152170

Hom.:

41770

Cov.:

AF XY:

0.727

AC XY:

54077

AN XY:

74396

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1431

2863

4294

5726

7157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.2

(source)

DANN

Benign

0.58

PhyloP100

0.099

PromoterAI

0.070

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over