Genetic Variant DRD4:c.285+33C>T (chr11-637622-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_000797.4(DRD4):c.285+33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0587 in 1,538,546 control chromosomes in the GnomAD database, including 3,141 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 0.050 ( 268 hom., cov: 33)

Exomes 𝑓: 0.060 ( 2873 hom. )

Consequence

DRD4
NM_000797.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.880

Publications

14 publications found

Variant links:

Genes affected

DRD4 (HGNC:3025): (dopamine receptor D4) This gene encodes the D4 subtype of the dopamine receptor. The D4 subtype is a G-protein coupled receptor which inhibits adenylyl cyclase. It is a target for drugs which treat schizophrenia and Parkinson disease. Mutations in this gene have been associated with various behavioral phenotypes, including autonomic nervous system dysfunction, attention deficit/hyperactivity disorder, and the personality trait of novelty seeking. This gene contains a polymorphic number (2-10 copies) of tandem 48 nt repeats; the sequence shown contains four repeats. [provided by RefSeq, Jul 2008]

DRD4 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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000797.4. 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
	DRD4	NM_000797.4	MANE Select	c.285+33C>T		intron	N/A	NP_000788.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD4	ENST00000176183.6	TSL:1 MANE Select	c.285+33C>T		intron	N/A	ENSP00000176183.5	P21917

Frequencies

GnomAD3 genomes

AF:

0.0499

AC:

7597

AN:

152176

Hom.:

269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0459

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.0886

Gnomad FIN

AF:

0.0574

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0564

Gnomad OTH

AF:

0.0655

GnomAD2 exomes

AF:

0.0636

AC:

9053

AN:

142406

AF XY:

0.0662

show subpopulations

Gnomad AFR exome

AF:

0.0198

Gnomad AMR exome

AF:

0.0321

Gnomad ASJ exome

AF:

0.0215

Gnomad EAS exome

AF:

0.195

Gnomad FIN exome

AF:

0.0583

Gnomad NFE exome

AF:

0.0574

Gnomad OTH exome

AF:

0.0650

GnomAD4 exome

AF:

0.0597

AC:

82742

AN:

1386250

Hom.:

2873

Cov.:

AF XY:

0.0603

AC XY:

41237

AN XY:

684214

show subpopulations

African (AFR)

AF:

0.0185

AC:

583

AN:

31586

American (AMR)

AF:

0.0342

AC:

1222

AN:

35710

Ashkenazi Jewish (ASJ)

AF:

0.0224

AC:

564

AN:

25154

East Asian (EAS)

AF:

0.142

AC:

5089

AN:

35748

South Asian (SAS)

AF:

0.0843

AC:

6677

AN:

79230

European-Finnish (FIN)

AF:

0.0603

AC:

2228

AN:

36928

Middle Eastern (MID)

AF:

0.0646

AC:

333

AN:

5152

European-Non Finnish (NFE)

AF:

0.0576

AC:

62099

AN:

1078896

Other (OTH)

AF:

0.0682

AC:

3947

AN:

57846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

4558

9115

13673

18230

22788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2408

4816

7224

9632

12040

<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:

0.0499

AC:

7593

AN:

152296

Hom.:

268

Cov.:

AF XY:

0.0506

AC XY:

3768

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0215

AC:

893

AN:

41586

American (AMR)

AF:

0.0458

AC:

700

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0190

AC:

AN:

3472

East Asian (EAS)

AF:

0.172

AC:

891

AN:

5166

South Asian (SAS)

AF:

0.0878

AC:

424

AN:

4828

European-Finnish (FIN)

AF:

0.0574

AC:

609

AN:

10616

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0564

AC:

3837

AN:

68008

Other (OTH)

AF:

0.0643

AC:

136

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

374

749

1123

1498

1872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0542

Hom.:

681

Bravo

AF:

0.0476

Asia WGS

AF:

0.121

AC:

422

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.5

(source)

DANN

Benign

0.89

PhyloP100

-0.88

PromoterAI

0.090

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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