Genetic Variant DRD4:p.Ala26_Gly29del (chr11-637361-CGCGGGGGCATCT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3BP6BA1

The NM_000797.4(DRD4):c.76_87delGCATCTGCGGGG(p.Ala26_Gly29del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 1,315,434 control chromosomes in the GnomAD database, including 3,567 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.067 ( 413 hom., cov: 31)

Exomes 𝑓: 0.072 ( 3154 hom. )

Consequence

DRD4
NM_000797.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.873

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_000797.4

BP6

Variant 11-637361-CGCGGGGGCATCT-C is Benign according to our data. Variant chr11-637361-CGCGGGGGCATCT-C is described in ClinVar as [Benign]. Clinvar id is 3059869.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD4	NM_000797.4 link	c.76_87delGCATCTGCGGGG	p.Ala26_Gly29del	conservative_inframe_deletion	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.76_87delGCATCTGCGGGG	p.Ala26_Gly29del	conservative_inframe_deletion	Exon 1 of 4	1	NM_000797.4	ENSP00000176183.5		P21917

Frequencies

GnomAD3 genomes

AF:

0.0666

AC:

10063

AN:

151102

Hom.:

407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0299

Gnomad AMI

AF:

0.0297

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.0624

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.0794

Gnomad FIN

AF:

0.0497

Gnomad MID

AF:

0.0701

Gnomad NFE

AF:

0.0705

Gnomad OTH

AF:

0.0511

GnomAD3 exomes

AF:

0.109

AC:

220

AN:

2014

Hom.:

AF XY:

0.104

AC XY:

135

AN XY:

1298

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.160

Gnomad ASJ exome

AF:

0.0476

Gnomad EAS exome

AF:

0.297

Gnomad SAS exome

AF:

0.0874

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.0967

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.0718

AC:

83631

AN:

1164224

Hom.:

3154

AF XY:

0.0722

AC XY:

40568

AN XY:

561832

show subpopulations

Gnomad4 AFR exome

AF:

0.0259

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.0654

Gnomad4 EAS exome

AF:

0.152

Gnomad4 SAS exome

AF:

0.0782

Gnomad4 FIN exome

AF:

0.0567

Gnomad4 NFE exome

AF:

0.0705

Gnomad4 OTH exome

AF:

0.0717

GnomAD4 genome

AF:

0.0667

AC:

10088

AN:

151210

Hom.:

413

Cov.:

AF XY:

0.0690

AC XY:

5099

AN XY:

73906

show subpopulations

Gnomad4 AFR

AF:

0.0301

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.0624

Gnomad4 EAS

AF:

0.155

Gnomad4 SAS

AF:

0.0790

Gnomad4 FIN

AF:

0.0497

Gnomad4 NFE

AF:

0.0705

Gnomad4 OTH

AF:

0.0558

Bravo

AF:

0.0680

Asia WGS

AF:

0.136

AC:

463

AN:

3428

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DRD4-related disorder

Benign:1

Jul 20, 2024

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

Splicing

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.

11-637361-CGCGGGGGCATCTGCGGGGGCATCT-CGCGGGGGCATCT

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