rs12749204

Variant names:

• chr1-28849701-A-G
• rs12749204
• NM_000911.4:c.228-9253A>G

Variant summary

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

The NM_000911.4(OPRD1):​c.228-9253A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,234 control chromosomes in the GnomAD database, including 2,358 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 0.16 (2358 hom., cov: 32)
• Consequence: OPRD1 NM_000911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486
• Publications: 12 publications found

Genes affected

OPRD1 (HGNC:8153): (opioid receptor delta 1) Enables G protein-coupled enkephalin receptor activity. Involved in several processes, including G protein-coupled opioid receptor signaling pathway; cellular response to hypoxia; and positive regulation of peptidyl-serine phosphorylation. Is intrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.228-9253A>G		intron_variant	Intron 1 of 2	ENST00000234961.7	NP_000902.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRD1	ENST00000234961.7	c.228-9253A>G		intron_variant	Intron 1 of 2	1	NM_000911.4	ENSP00000234961.2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24765 AN: 152116 Hom.: 2359 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.0440

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.163 AC: 24776 AN: 152234 Hom.: 2358 Cov.: 32 AF XY: 0.165 AC XY: 12310 AN XY: 74434

African (AFR) AF: 0.0763 AC: 3172 AN: 41580

American (AMR) AF: 0.239 AC: 3652 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 850 AN: 3472

East Asian (EAS) AF: 0.0439 AC: 228 AN: 5190

South Asian (SAS) AF: 0.142 AC: 686 AN: 4830

European-Finnish (FIN) AF: 0.237 AC: 2513 AN: 10588

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13102 AN: 67988

Other (OTH) AF: 0.193 AC: 408 AN: 2116

Alfa AF: 0.184 Hom.: 11464

Bravo AF: 0.162

Asia WGS AF: 0.109 AC: 376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.1
DANN	Benign	0.65
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12749204; hg19: chr1-29176213;