chr11-637361-CGCGGGGGCATCT-C

Variant names:

• chr11-637361-CGCGGGGGCATCT-C
• rs572586776
• NM_000797.4:c.76_87delGCATCTGCGGGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP3 BP6 BA1

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. 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 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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.873
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.76_87delGCATCTGCGGGG	p.Ala26_Gly29del	conservative_inframe_deletion	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.76_87delGCATCTGCGGGG	p.Ala26_Gly29del	conservative_inframe_deletion	Exon 1 of 4	ENSP00000176183.5	P21917

Frequencies

GnomAD3 genomes AF: 0.0666 AC: 10063 AN: 151102 Hom.: 407 Cov.: 31

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

GnomAD2 exomes AF: 0.109 AC: 220 AN: 2014 AF XY: 0.104

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 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

African (AFR) AF: 0.0259 AC: 598 AN: 23062

American (AMR) AF: 0.128 AC: 1131 AN: 8832

Ashkenazi Jewish (ASJ) AF: 0.0654 AC: 1006 AN: 15376

East Asian (EAS) AF: 0.152 AC: 4030 AN: 26500

South Asian (SAS) AF: 0.0782 AC: 3168 AN: 40514

European-Finnish (FIN) AF: 0.0567 AC: 1490 AN: 26270

Middle Eastern (MID) AF: 0.0527 AC: 170 AN: 3226

European-Non Finnish (NFE) AF: 0.0705 AC: 68628 AN: 972898

Other (OTH) AF: 0.0717 AC: 3410 AN: 47546

GnomAD4 genome AF: 0.0667 AC: 10088 AN: 151210 Hom.: 413 Cov.: 31 AF XY: 0.0690 AC XY: 5099 AN XY: 73906

African (AFR) AF: 0.0301 AC: 1246 AN: 41338

American (AMR) AF: 0.132 AC: 2006 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.0624 AC: 216 AN: 3462

East Asian (EAS) AF: 0.155 AC: 794 AN: 5112

South Asian (SAS) AF: 0.0790 AC: 380 AN: 4808

European-Finnish (FIN) AF: 0.0497 AC: 511 AN: 10290

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0705 AC: 4775 AN: 67724

Other (OTH) AF: 0.0558 AC: 117 AN: 2098

Alfa AF: 0.0259 Hom.: 6

Bravo AF: 0.0680

Asia WGS AF: 0.136 AC: 463 AN: 3428

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DRD4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.87
Mutation Taster		=195/5	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs572586776; hg19: chr11-637361; COSMIC: COSV51562238; COSMIC: COSV51562238;