rs4274224

chr11-113448730-G-Achr11-113448730-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• 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/exons	MANE	UniProt
DRD2	NM_000795.4	c.-31-24048C>T		intron_variant		ENST00000362072.8
DRD2	NM_016574.4	c.-31-24048C>T		intron_variant
DRD2	XM_017017296.3	c.-31-24048C>T		intron_variant
DRD2	XM_047426511.1	c.-31-24048C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD2	ENST00000362072.8	c.-31-24048C>T		intron_variant		1	NM_000795.4	P4
DRD2	ENST00000346454.7	c.-31-24048C>T		intron_variant		1
DRD2	ENST00000540600.5	n.35-24048C>T		intron_variant, non_coding_transcript_variant		1
DRD2	ENST00000542616.1	c.-31-24048C>T		intron_variant		4

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

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.482

Alfa AF: 0.523 Hom.: 9690

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

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: rs4274224; hg19: chr11-113319452;