11-637536-GCCGCCGACCTCCT-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_000797.4(DRD4):​c.235_247delGCCGACCTCCTCC​(p.Ala79SerfsTer21) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,564,018 control chromosomes in the GnomAD database, including 170 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.010 ( 17 hom., cov: 32)
Exomes 𝑓: 0.013 ( 153 hom. )

Consequence

DRD4
NM_000797.4 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter P:1B:3

Conservation

PhyloP100: 7.73
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 -6 ACMG points.

BP6
Variant 11-637536-GCCGCCGACCTCCT-G is Benign according to our data. Variant chr11-637536-GCCGCCGACCTCCT-G is described in ClinVar as [Benign]. Clinvar id is 16767.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-637536-GCCGCCGACCTCCT-G is described in Lovd as [Benign]. Variant chr11-637536-GCCGCCGACCTCCT-G is described in Lovd as [Likely_benign].
BS2
High AC in GnomAd4 at 1545 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DRD4NM_000797.4 linkc.235_247delGCCGACCTCCTCC p.Ala79SerfsTer21 frameshift_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.235_247delGCCGACCTCCTCC p.Ala79SerfsTer21 frameshift_variant Exon 1 of 4 1 NM_000797.4 ENSP00000176183.5 P21917

Frequencies

GnomAD3 genomes
AF:
0.0102
AC:
1545
AN:
152146
Hom.:
17
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00186
Gnomad AMI
AF:
0.00989
Gnomad AMR
AF:
0.00183
Gnomad ASJ
AF:
0.00750
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0411
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0141
Gnomad OTH
AF:
0.00525
GnomAD3 exomes
AF:
0.00771
AC:
1319
AN:
171114
Hom.:
14
AF XY:
0.00756
AC XY:
701
AN XY:
92706
show subpopulations
Gnomad AFR exome
AF:
0.000770
Gnomad AMR exome
AF:
0.00167
Gnomad ASJ exome
AF:
0.00503
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000207
Gnomad FIN exome
AF:
0.0279
Gnomad NFE exome
AF:
0.0121
Gnomad OTH exome
AF:
0.00935
GnomAD4 exome
AF:
0.0126
AC:
17828
AN:
1411754
Hom.:
153
AF XY:
0.0123
AC XY:
8616
AN XY:
698834
show subpopulations
Gnomad4 AFR exome
AF:
0.00147
Gnomad4 AMR exome
AF:
0.00173
Gnomad4 ASJ exome
AF:
0.00595
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000248
Gnomad4 FIN exome
AF:
0.0365
Gnomad4 NFE exome
AF:
0.0142
Gnomad4 OTH exome
AF:
0.00971
GnomAD4 genome
AF:
0.0101
AC:
1545
AN:
152264
Hom.:
17
Cov.:
32
AF XY:
0.0109
AC XY:
809
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.00185
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00750
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0411
Gnomad4 NFE
AF:
0.0141
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.0115
Hom.:
3
Bravo
AF:
0.00736

ClinVar

Significance: Benign
Submissions summary: Pathogenic:1Benign:3
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:2
-
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Jan 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

DRD4: BS1, BS2 -

AUTONOMIC NERVOUS SYSTEM DYSFUNCTION Pathogenic:1
Dec 01, 1994
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only

- -

not specified Benign:1
-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

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.

Other links and lift over

dbSNP: rs587776842; hg19: chr11-637536; API