dbSNP rs7124601: DRD4:c.286-160C>A (chr11-639273-C-A) – 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.286-160C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 663,228 control chromosomes in the GnomAD database, including 69,681 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 0.47 ( 17029 hom., cov: 30)

Exomes 𝑓: 0.45 ( 52652 hom. )

Consequence

DRD4
NM_000797.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.45

Publications

12 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:

Genome browser will be placed here

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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD4	NM_000797.4 link	c.286-160C>A		intron_variant	Intron 1 of 3	ENST00000176183.6	NP_000788.2	P21917

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD4	ENST00000176183.6 link	c.286-160C>A		intron_variant	Intron 1 of 3	1	NM_000797.4	ENSP00000176183.5		P21917
DRD4	ENST00000528733.1 link	n.102+115C>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71254

AN:

151562

Hom.:

17019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.532

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.467

Gnomad OTH

AF:

0.486

GnomAD4 exome

AF:

0.447

AC:

228645

AN:

511546

Hom.:

52652

Cov.:

AF XY:

0.446

AC XY:

121282

AN XY:

271892

show subpopulations

African (AFR)

AF:

0.525

AC:

7434

AN:

14156

American (AMR)

AF:

0.452

AC:

13221

AN:

29270

Ashkenazi Jewish (ASJ)

AF:

0.508

AC:

8291

AN:

16326

East Asian (EAS)

AF:

0.209

AC:

6140

AN:

29418

South Asian (SAS)

AF:

0.428

AC:

24198

AN:

56524

European-Finnish (FIN)

AF:

0.437

AC:

13111

AN:

29982

Middle Eastern (MID)

AF:

0.500

AC:

1090

AN:

2180

European-Non Finnish (NFE)

AF:

0.465

AC:

142197

AN:

306118

Other (OTH)

AF:

0.470

AC:

12963

AN:

27572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5895

11790

17686

23581

29476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1242

2484

3726

4968

6210

<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:

0.470

AC:

71294

AN:

151682

Hom.:

17029

Cov.:

AF XY:

0.465

AC XY:

34453

AN XY:

74112

show subpopulations

African (AFR)

AF:

0.532

AC:

21993

AN:

41376

American (AMR)

AF:

0.443

AC:

6751

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

1769

AN:

3468

East Asian (EAS)

AF:

0.239

AC:

1229

AN:

5144

South Asian (SAS)

AF:

0.412

AC:

1981

AN:

4804

European-Finnish (FIN)

AF:

0.424

AC:

4454

AN:

10506

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.467

AC:

31647

AN:

67838

Other (OTH)

AF:

0.486

AC:

1025

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1874

3748

5621

7495

9369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.413

Hom.:

2210

Bravo

AF:

0.475

Asia WGS

AF:

0.368

AC:

1280

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.91

(source)

DANN

Benign

0.68

PhyloP100

-2.4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over