NM_000797.4:c.31G>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_000797.4(DRD4):​c.31G>T​(p.Gly11Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000629 in 1,112,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

DRD4
NM_000797.4 missense

Scores

3
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.37
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.30253807).
BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DRD4NM_000797.4 linkc.31G>T p.Gly11Trp missense_variant Exon 1 of 4 ENST00000176183.6 NP_000788.2 P21917

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DRD4ENST00000176183.6 linkc.31G>T p.Gly11Trp missense_variant Exon 1 of 4 1 NM_000797.4 ENSP00000176183.5 P21917

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000629
AC:
7
AN:
1112418
Hom.:
0
Cov.:
31
AF XY:
0.00000751
AC XY:
4
AN XY:
532384
show subpopulations
Gnomad4 AFR exome
AF:
0.000225
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000448
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
9.6
DANN
Benign
0.65
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.022
N
M_CAP
Pathogenic
0.95
D
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-0.92
T
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-0.19
N
REVEL
Benign
0.099
Sift
Benign
0.058
T
Sift4G
Pathogenic
0.0
D
Vest4
0.25
MutPred
0.35
Loss of disorder (P = 0.0132);
MVP
0.67
MPC
0.33
ClinPred
0.79
D
GERP RS
-2.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
gMVP
0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs189482961; hg19: chr11-637335; API