11-113447251-T-C

Variant names:

• chr11-113447251-T-C
• rs4245146
• NM_000795.4:c.-31-22569A>G

Variant summary

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

The NM_000795.4(DRD2):​c.-31-22569A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,108 control chromosomes in the GnomAD database, including 20,286 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 0.49 (20286 hom., cov: 32)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685
• Publications: 20 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4	c.-31-22569A>G		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.-31-22569A>G		intron_variant	Intron 1 of 7	1	NM_000795.4	ENSP00000354859.3

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75111 AN: 151990 Hom.: 20270 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.494 AC: 75175 AN: 152108 Hom.: 20286 Cov.: 32 AF XY: 0.512 AC XY: 38059 AN XY: 74374

African (AFR) AF: 0.285 AC: 11845 AN: 41492

American (AMR) AF: 0.544 AC: 8322 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1775 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4237 AN: 5166

South Asian (SAS) AF: 0.641 AC: 3085 AN: 4812

European-Finnish (FIN) AF: 0.765 AC: 8099 AN: 10588

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36140 AN: 67970

Other (OTH) AF: 0.484 AC: 1023 AN: 2114

Alfa AF: 0.507 Hom.: 25431

Bravo AF: 0.467

Asia WGS AF: 0.685 AC: 2379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.32
PhyloP100		-0.69
PromoterAI		-0.016	Neutral
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: rs4245146; hg19: chr11-113317973;