rs508448

Positions:

• chr1-28855013-A-G

Variant summary

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

The NM_000911.4(OPRD1):​c.228-3941A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,930 control chromosomes in the GnomAD database, including 18,751 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 (18751 hom., cov: 31)
• Consequence: OPRD1 NM_000911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRD1	NM_000911.4	c.228-3941A>G		intron_variant		ENST00000234961.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRD1	ENST00000234961.7	c.228-3941A>G		intron_variant		1	NM_000911.4	P1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74890 AN: 151812 Hom.: 18725 Cov.: 31

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.493 AC: 74964 AN: 151930 Hom.: 18751 Cov.: 31 AF XY: 0.498 AC XY: 36976 AN XY: 74248

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.765

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.467

Alfa AF: 0.486 Hom.: 39232

Bravo AF: 0.500

Asia WGS AF: 0.655 AC: 2279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.65

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: rs508448; hg19: chr1-29181525;