Genetic Variant DRD3:c.723+146G>A (chr3-114139354-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000796.6(DRD3):c.723+146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 760,540 control chromosomes in the GnomAD database, including 25,568 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 0.21 ( 3969 hom., cov: 33)

Exomes 𝑓: 0.26 ( 21599 hom. )

Consequence

DRD3
NM_000796.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.213

Publications

55 publications found

Variant links:

Genes affected

DRD3 (HGNC:3024): (dopamine receptor D3) This gene encodes the D3 subtype of the five (D1-D5) dopamine receptors. The activity of the D3 subtype receptor is mediated by G proteins which inhibit adenylyl cyclase. This receptor is localized to the limbic areas of the brain, which are associated with cognitive, emotional, and endocrine functions. Genetic variation in this gene may be associated with susceptibility to hereditary essential tremor 1. Alternative splicing of this gene results in transcript variants encoding different isoforms, although some variants may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]

DRD3 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000796.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DRD3	NM_000796.6	MANE Select	c.723+146G>A	intron	N/A	NP_000787.2	X5D2G4
DRD3	NM_001282563.2		c.723+146G>A	intron	N/A	NP_001269492.1	P35462-1
DRD3	NM_001290809.1		c.723+146G>A	intron	N/A	NP_001277738.1	X5D2G4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DRD3	ENST00000383673.5	TSL:1 MANE Select	c.723+146G>A	intron	N/A	ENSP00000373169.2	P35462-1
DRD3	ENST00000467632.5	TSL:1	c.723+146G>A	intron	N/A	ENSP00000420662.1	P35462-1
DRD3	ENST00000460779.5	TSL:2	c.723+146G>A	intron	N/A	ENSP00000419402.1	P35462-1

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31661

AN:

152070

Hom.:

3971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0633

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.246

GnomAD4 exome

AF:

0.261

AC:

158527

AN:

608352

Hom.:

21599

AF XY:

0.262

AC XY:

82222

AN XY:

313634

show subpopulations

African (AFR)

AF:

0.0589

AC:

974

AN:

16524

American (AMR)

AF:

0.217

AC:

4877

AN:

22438

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

5343

AN:

14190

East Asian (EAS)

AF:

0.298

AC:

10192

AN:

34226

South Asian (SAS)

AF:

0.273

AC:

11315

AN:

41430

European-Finnish (FIN)

AF:

0.285

AC:

10240

AN:

35928

Middle Eastern (MID)

AF:

0.325

AC:

712

AN:

2192

European-Non Finnish (NFE)

AF:

0.260

AC:

106684

AN:

410272

Other (OTH)

AF:

0.263

AC:

8190

AN:

31152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

5535

11070

16605

22140

27675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2066

4132

6198

8264

10330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.208

AC:

31654

AN:

152188

Hom.:

3969

Cov.:

AF XY:

0.211

AC XY:

15673

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0631

AC:

2624

AN:

41552

American (AMR)

AF:

0.235

AC:

3588

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

1291

AN:

3472

East Asian (EAS)

AF:

0.270

AC:

1399

AN:

5174

South Asian (SAS)

AF:

0.264

AC:

1277

AN:

4830

European-Finnish (FIN)

AF:

0.268

AC:

2829

AN:

10568

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17910

AN:

67994

Other (OTH)

AF:

0.244

AC:

514

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1238

2476

3714

4952

6190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.243

Hom.:

2851

Bravo

AF:

0.198

Asia WGS

AF:

0.265

AC:

921

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.9

(source)

DANN

Benign

0.76

PhyloP100

-0.21

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over