rs4581480

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4	c.-32+21324G>A		intron_variant	Intron 1 of 7	ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.-32+21324G>A		intron_variant	Intron 1 of 6		NP_057658.2
DRD2	XM_017017296.3	c.-32+20478G>A		intron_variant	Intron 1 of 7		XP_016872785.1
DRD2	XM_047426511.1	c.-32+20478G>A		intron_variant	Intron 1 of 6		XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.-32+21324G>A		intron_variant	Intron 1 of 7	1	NM_000795.4	ENSP00000354859.3
DRD2	ENST00000346454.7	c.-32+21324G>A		intron_variant	Intron 1 of 6	1		ENSP00000278597.5
DRD2	ENST00000540600.5	n.34+21906G>A		intron_variant	Intron 1 of 5	1
DRD2	ENST00000542616.1	c.-32+20478G>A		intron_variant	Intron 2 of 2	4		ENSP00000441474.1

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

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.853

Gnomad4 ASJ AF: 0.939

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.889

Gnomad4 FIN AF: 0.942

Gnomad4 NFE AF: 0.902

Gnomad4 OTH AF: 0.829

Alfa AF: 0.870 Hom.: 29253

Bravo AF: 0.763

Asia WGS AF: 0.828 AC: 2879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.4
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs4581480; hg19: chr11-113324474;