dbSNP rs587776842: DRD4:p.Ala79SerfsTer21 (chr11-637536-GCCGCCGACCTCCT-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely 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/Likely benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: 7.73

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 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/Likely_benign. ClinVar VariationId is 16767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1545 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000797.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD4	NM_000797.4	MANE Select	c.235_247delGCCGACCTCCTCC	p.Ala79SerfsTer21	frameshift	Exon 1 of 4	NP_000788.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD4	ENST00000176183.6	TSL:1 MANE Select	c.235_247delGCCGACCTCCTCC	p.Ala79SerfsTer21	frameshift	Exon 1 of 4	ENSP00000176183.5	P21917

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1545

AN:

152146

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00771

AC:

1319

AN:

171114

AF XY:

0.00756

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 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

African (AFR)

AF:

0.00147

AC:

AN:

32552

American (AMR)

AF:

0.00173

AC:

AN:

38232

Ashkenazi Jewish (ASJ)

AF:

0.00595

AC:

151

AN:

25388

East Asian (EAS)

AF:

0.00

AC:

AN:

37336

South Asian (SAS)

AF:

0.000248

AC:

AN:

80684

European-Finnish (FIN)

AF:

0.0365

AC:

1513

AN:

41468

Middle Eastern (MID)

AF:

0.00141

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.0142

AC:

15452

AN:

1091678

Other (OTH)

AF:

0.00971

AC:

570

AN:

58724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

1196

2392

3588

4784

5980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

554

1108

1662

2216

2770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0101

AC:

1545

AN:

152264

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

809

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

41560

American (AMR)

AF:

0.00183

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00750

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0411

AC:

436

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0141

AC:

958

AN:

68004

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

148

221

295

369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0115

Hom.:

Bravo

AF:

0.00736

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

AUTONOMIC NERVOUS SYSTEM DYSFUNCTION (1)

DRD4-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

7.7

Mutation Taster

=11/189

disease causing (ClinVar)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over