Genetic Variant DRD3:c.384-147T>C (chr3-114147704-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_000796.6(DRD3):c.384-147T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 931,338 control chromosomes in the GnomAD database, including 6,573 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 0.12 ( 1209 hom., cov: 31)

Exomes 𝑓: 0.11 ( 5364 hom. )

Consequence

DRD3
NM_000796.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0990

Publications

9 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=-0.93).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.159 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
DRD3	NM_000796.6	MANE Select	c.384-147T>C	intron	N/A	NP_000787.2
DRD3	NM_001282563.2		c.384-147T>C	intron	N/A	NP_001269492.1
DRD3	NM_001290809.1		c.384-147T>C	intron	N/A	NP_001277738.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DRD3	ENST00000383673.5	TSL:1 MANE Select	c.384-147T>C	intron	N/A	ENSP00000373169.2
DRD3	ENST00000467632.5	TSL:1	c.384-147T>C	intron	N/A	ENSP00000420662.1
DRD3	ENST00000460779.5	TSL:2	c.384-147T>C	intron	N/A	ENSP00000419402.1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18497

AN:

152038

Hom.:

1206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.0909

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.0675

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.117

GnomAD4 exome

AF:

0.110

AC:

85450

AN:

779182

Hom.:

5364

AF XY:

0.112

AC XY:

43680

AN XY:

390326

show subpopulations

African (AFR)

AF:

0.153

AC:

2863

AN:

18690

American (AMR)

AF:

0.0654

AC:

1521

AN:

23264

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

2171

AN:

16168

East Asian (EAS)

AF:

0.135

AC:

4286

AN:

31792

South Asian (SAS)

AF:

0.173

AC:

8493

AN:

49192

European-Finnish (FIN)

AF:

0.0648

AC:

2560

AN:

39478

Middle Eastern (MID)

AF:

0.173

AC:

446

AN:

2572

European-Non Finnish (NFE)

AF:

0.105

AC:

58751

AN:

561430

Other (OTH)

AF:

0.119

AC:

4359

AN:

36596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

3642

7285

10927

14570

18212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1742

3484

5226

6968

8710

<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:

0.122

AC:

18513

AN:

152156

Hom.:

1209

Cov.:

AF XY:

0.122

AC XY:

9086

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.157

AC:

6511

AN:

41530

American (AMR)

AF:

0.0907

AC:

1383

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

468

AN:

3470

East Asian (EAS)

AF:

0.115

AC:

598

AN:

5182

South Asian (SAS)

AF:

0.169

AC:

813

AN:

4818

European-Finnish (FIN)

AF:

0.0675

AC:

715

AN:

10586

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7615

AN:

68000

Other (OTH)

AF:

0.116

AC:

245

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

821

1641

2462

3282

4103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

218

436

654

872

1090

<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:

0.116

Hom.:

186

Bravo

AF:

0.123

Asia WGS

AF:

0.139

AC:

483

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

3.2

(source)

DANN

Benign

0.63

PhyloP100

0.099

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