rs2236861

Positions:

• chr1-28813244-G-A
• chr1-28813244-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000911.4(OPRD1):​c.227+634G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,164 control chromosomes in the GnomAD database, including 3,189 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 0.19 (3189 hom., cov: 32)
• Consequence: OPRD1 NM_000911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.227+634G>A		intron_variant		ENST00000234961.7	NP_000902.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRD1	ENST00000234961.7	c.227+634G>A		intron_variant		1	NM_000911.4	ENSP00000234961	P1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28763 AN: 152046 Hom.: 3190 Cov.: 32

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.189 AC: 28768 AN: 152164 Hom.: 3189 Cov.: 32 AF XY: 0.192 AC XY: 14290 AN XY: 74386

Gnomad4 AFR AF: 0.0828

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.209

Alfa AF: 0.225 Hom.: 6441

Bravo AF: 0.179

Asia WGS AF: 0.132 AC: 457 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	0.18
DANN	Benign	0.70

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: rs2236861; hg19: chr1-29139756;