11-113448730-G-A

Variant names:

• chr11-113448730-G-A
• rs4274224
• NM_000795.4:c.-31-24048C>T

Variant summary

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

The NM_000795.4(DRD2):​c.-31-24048C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,890 control chromosomes in the GnomAD database, including 20,338 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 0.50 (20338 hom., cov: 31)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 44 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4	c.-31-24048C>T		intron_variant	Intron 1 of 7	ENST00000362072.8	NP_000786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.-31-24048C>T		intron_variant	Intron 1 of 7	1	NM_000795.4	ENSP00000354859.3
DRD2	ENST00000346454.7	c.-31-24048C>T		intron_variant	Intron 1 of 6	1		ENSP00000278597.5
DRD2	ENST00000540600.5	n.35-24048C>T		intron_variant	Intron 1 of 5	1
DRD2	ENST00000542616.1	c.-31-24048C>T		intron_variant	Intron 2 of 2	4		ENSP00000441474.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75569 AN: 151772 Hom.: 20321 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.498 AC: 75634 AN: 151890 Hom.: 20338 Cov.: 31 AF XY: 0.515 AC XY: 38221 AN XY: 74226

African (AFR) AF: 0.305 AC: 12626 AN: 41404

American (AMR) AF: 0.538 AC: 8211 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1764 AN: 3466

East Asian (EAS) AF: 0.819 AC: 4208 AN: 5136

South Asian (SAS) AF: 0.641 AC: 3083 AN: 4806

European-Finnish (FIN) AF: 0.763 AC: 8064 AN: 10566

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36012 AN: 67928

Other (OTH) AF: 0.482 AC: 1016 AN: 2110

Alfa AF: 0.520 Hom.: 10768

Bravo AF: 0.470

Asia WGS AF: 0.689 AC: 2391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.63
DANN	Benign	0.55
PhyloP100		-1.1
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: rs4274224; hg19: chr11-113319452;