11-637335-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000797.4(DRD4):c.31G>C(p.Gly11Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,263,252 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 11 hom., cov: 32)

Exomes 𝑓: 0.013 ( 109 hom. )

Consequence

DRD4
NM_000797.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

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]

DRD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011060178).

BP6

Variant 11-637335-G-C is Benign according to our data. Variant chr11-637335-G-C is described in ClinVar as [Benign]. Clinvar id is 787592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1208 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD4	NM_000797.4 link	c.31G>C	p.Gly11Arg	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
DRD4	ENST00000176183.6 link	c.31G>C	p.Gly11Arg	missense_variant	Exon 1 of 4	1	NM_000797.4	ENSP00000176183.5		P21917

Frequencies

GnomAD3 genomes

AF:

0.00801

AC:

1208

AN:

150758

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00238

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00337

Gnomad ASJ

AF:

0.00434

Gnomad EAS

AF:

0.000391

Gnomad SAS

AF:

0.000832

Gnomad FIN

AF:

0.0117

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0134

Gnomad OTH

AF:

0.00483

GnomAD3 exomes

AF:

0.00365

AC:

AN:

2738

Hom.:

AF XY:

0.00323

AC XY:

AN XY:

1856

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00657

Gnomad OTH exome

AF:

0.0125

GnomAD4 exome

AF:

0.0127

AC:

14106

AN:

1112386

Hom.:

109

Cov.:

AF XY:

0.0126

AC XY:

6720

AN XY:

532366

show subpopulations

Gnomad4 AFR exome

AF:

0.000899

Gnomad4 AMR exome

AF:

0.00349

Gnomad4 ASJ exome

AF:

0.00241

Gnomad4 EAS exome

AF:

0.0000405

Gnomad4 SAS exome

AF:

0.00213

Gnomad4 FIN exome

AF:

0.0116

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.00801

AC:

1208

AN:

150866

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

563

AN XY:

73730

show subpopulations

Gnomad4 AFR

AF:

0.00237

Gnomad4 AMR

AF:

0.00337

Gnomad4 ASJ

AF:

0.00434

Gnomad4 EAS

AF:

0.000392

Gnomad4 SAS

AF:

0.000833

Gnomad4 FIN

AF:

0.0117

Gnomad4 NFE

AF:

0.0134

Gnomad4 OTH

AF:

0.00478

Alfa

AF:

0.00494

Hom.:

Bravo

AF:

0.00706

ExAC

AF:

0.000566

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DRD4: BS1, BS2 -

Sep 03, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

DRD4-related disorder

Benign:1

Jul 09, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.4

DANN

Benign

0.87

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.023

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.1

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.52

REVEL

Benign

0.049

Sift

Uncertain

0.0070

Sift4G

Pathogenic

0.0

Vest4

0.16

MutPred

0.17

Gain of MoRF binding (P = 0.0032);

MVP

0.45

MPC

0.34

ClinPred

0.068

GERP RS

-2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

gMVP

0.55

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over