rs4581480

Variant names:

• chr11-113453752-C-T
• rs4581480
• NM_000795.4:c.-32+21324G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000795.4(DRD2):​c.-32+21324G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,170 control chromosomes in the GnomAD database, including 49,352 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (49352 hom., cov: 33)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294
• Publications: 31 publications found

Genes affected

DRD2 (HGNC:3023): (dopamine receptor D2) This gene encodes the D2 subtype of the dopamine receptor. This G-protein coupled receptor inhibits adenylyl cyclase activity. A missense mutation in this gene causes myoclonus dystonia; other mutations have been associated with schizophrenia. Alternative splicing of this gene results in two transcript variants encoding different isoforms. A third variant has been described, but it has not been determined whether this form is normal or due to aberrant splicing. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000795.4. 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
	DRD2	NM_000795.4	MANE Select	c.-32+21324G>A		intron	N/A	NP_000786.1	P14416-1
	DRD2	NM_001440368.1		c.-32+21324G>A		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.-32+21324G>A		intron	N/A	NP_057658.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	ENST00000362072.8	TSL:1 MANE Select	c.-32+21324G>A		intron	N/A	ENSP00000354859.3	P14416-1
	DRD2	ENST00000346454.7	TSL:1	c.-32+21324G>A		intron	N/A	ENSP00000278597.5	P14416-2
	DRD2	ENST00000540600.5	TSL:1	n.34+21906G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119043 AN: 152052 Hom.: 49334 Cov.: 33

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.832

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.783 AC: 119109 AN: 152170 Hom.: 49352 Cov.: 33 AF XY: 0.789 AC XY: 58737 AN XY: 74404

African (AFR) AF: 0.483 AC: 20004 AN: 41444

American (AMR) AF: 0.853 AC: 13058 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 3261 AN: 3472

East Asian (EAS) AF: 0.847 AC: 4379 AN: 5172

South Asian (SAS) AF: 0.889 AC: 4280 AN: 4816

European-Finnish (FIN) AF: 0.942 AC: 10005 AN: 10622

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.902 AC: 61334 AN: 68026

Other (OTH) AF: 0.829 AC: 1750 AN: 2110

Alfa AF: 0.808 Hom.: 41368

Bravo AF: 0.763

Asia WGS AF: 0.828 AC: 2879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.4
DANN	Benign	0.45
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4581480; hg19: chr11-113324474;