Genetic Variant DRD4:p.Gly41Val (chr11-637426-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000797.4(DRD4):c.122G>T(p.Gly41Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000779 in 1,526,918 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

DRD4
NM_000797.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.973

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 19 AD gene.

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.122G>T	p.Gly41Val	missense	Exon 1 of 4	NP_000788.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD4	ENST00000176183.6	TSL:1 MANE Select	c.122G>T	p.Gly41Val	missense	Exon 1 of 4	ENSP00000176183.5	P21917

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.0000877

AC:

AN:

125492

AF XY:

0.0000729

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.0000644

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000727

AC:

100

AN:

1374898

Hom.:

Cov.:

AF XY:

0.0000723

AC XY:

AN XY:

677800

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30690

American (AMR)

AF:

0.000169

AC:

AN:

35438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24868

East Asian (EAS)

AF:

0.00

AC:

AN:

35076

South Asian (SAS)

AF:

0.0000763

AC:

AN:

78654

European-Finnish (FIN)

AF:

0.0000298

AC:

AN:

33560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4306

European-Non Finnish (NFE)

AF:

0.0000781

AC:

AN:

1074928

Other (OTH)

AF:

0.0000523

AC:

AN:

57378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000125

AC:

AN:

152020

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41426

American (AMR)

AF:

0.000655

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67948

Other (OTH)

AF:

0.000958

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000174

ExAC

AF:

0.0000164

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.92

M_CAP

Pathogenic

0.95

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.64

PhyloP100

0.97

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.37

Sift

Benign

0.19

Sift4G

Uncertain

0.021

Vest4

0.51

MVP

0.88

MPC

0.35

ClinPred

0.15

GERP RS

2.4

PromoterAI

0.026

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.5

gMVP

0.70

Mutation Taster

=23/77

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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