NM_000911.4:c.227+22877C>A

Variant names:

• chr1-28835487-C-A
• rs2236855
• NM_000911.4:c.227+22877C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000911.4(OPRD1):​c.227+22877C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,168 control chromosomes in the GnomAD database, including 6,164 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 0.28 (6164 hom., cov: 32)
• Consequence: OPRD1 NM_000911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 13 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000911.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRD1	NM_000911.4	MANE Select	c.227+22877C>A		intron	N/A	NP_000902.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRD1	ENST00000234961.7	TSL:1 MANE Select	c.227+22877C>A		intron	N/A	ENSP00000234961.2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42361 AN: 152050 Hom.: 6163 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.279 AC: 42391 AN: 152168 Hom.: 6164 Cov.: 32 AF XY: 0.279 AC XY: 20768 AN XY: 74406

African (AFR) AF: 0.317 AC: 13142 AN: 41496

American (AMR) AF: 0.316 AC: 4823 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1042 AN: 3470

East Asian (EAS) AF: 0.100 AC: 519 AN: 5186

South Asian (SAS) AF: 0.191 AC: 920 AN: 4828

European-Finnish (FIN) AF: 0.292 AC: 3093 AN: 10588

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17879 AN: 67998

Other (OTH) AF: 0.306 AC: 647 AN: 2112

Alfa AF: 0.256 Hom.: 6784

Bravo AF: 0.287

Asia WGS AF: 0.168 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.88
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2236855; hg19: chr1-29161999;