NM_000911.4:c.227+8216C>T

Variant names:

• chr1-28820826-C-T
• rs536706
• NM_000911.4:c.227+8216C>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+8216C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,556 control chromosomes in the GnomAD database, including 17,724 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 0.46 (17724 hom., cov: 29)
• Consequence: OPRD1 NM_000911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.227+8216C>T		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.227+8216C>T		intron_variant	Intron 1 of 2	1	NM_000911.4	ENSP00000234961.2

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69241 AN: 151438 Hom.: 17717 Cov.: 29

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.457 AC: 69277 AN: 151556 Hom.: 17724 Cov.: 29 AF XY: 0.463 AC XY: 34269 AN XY: 74022

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.438

Alfa AF: 0.487 Hom.: 2411

Bravo AF: 0.435

Asia WGS AF: 0.669 AC: 2325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
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: rs536706; hg19: chr1-29147338;