11-637462-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_000797.4(DRD4):​c.158C>T​(p.Ser53Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000612 in 1,536,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

DRD4
NM_000797.4 missense

Scores

2
1
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0930
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 Benign. Variant got -7 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13892129).
BP6
Variant 11-637462-C-T is Benign according to our data. Variant chr11-637462-C-T is described in Lovd as [Likely_benign].
BS2
High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DRD4NM_000797.4 linkc.158C>T p.Ser53Leu 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.158C>T p.Ser53Leu missense_variant Exon 1 of 4 1 NM_000797.4 ENSP00000176183.5 P21917

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152112
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000659
AC:
9
AN:
136498
Hom.:
0
AF XY:
0.0000679
AC XY:
5
AN XY:
73626
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000816
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000134
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000563
AC:
78
AN:
1384294
Hom.:
0
Cov.:
32
AF XY:
0.0000600
AC XY:
41
AN XY:
683284
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000280
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000642
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000454
Gnomad4 OTH exome
AF:
0.0000691
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152112
Hom.:
0
Cov.:
33
AF XY:
0.0000673
AC XY:
5
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000907
ExAC
AF:
0.0000391
AC:
4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
19
DANN
Uncertain
0.99
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.065
N
M_CAP
Pathogenic
0.35
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.0
T
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
0.65
N
REVEL
Benign
0.026
Sift
Benign
0.12
T
Sift4G
Benign
0.22
T
Vest4
0.12
MutPred
0.47
Gain of stability (P = 0.1295);
MVP
0.35
MPC
0.25
ClinPred
0.070
T
GERP RS
1.4
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.2
gMVP
0.45

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: rs776495106; hg19: chr11-637462; API