1-28814643-G-A

Variant names:

• chr1-28814643-G-A
• rs533123
• NM_000911.4:c.227+2033G>A

Variant summary

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

The NM_000911.4(OPRD1):​c.227+2033G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,046 control chromosomes in the GnomAD database, including 42,982 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 0.74 (42982 hom., cov: 31)
• Consequence: OPRD1 NM_000911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 27 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]

ENSG00000305996 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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+2033G>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+2033G>A		intron	N/A	ENSP00000234961.2
	ENSG00000305996	ENST00000814652.1		n.92-13280G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111939 AN: 151928 Hom.: 42971 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.899

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.749

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

GnomAD4 genome AF: 0.737 AC: 111984 AN: 152046 Hom.: 42982 Cov.: 31 AF XY: 0.742 AC XY: 55172 AN XY: 74336

African (AFR) AF: 0.508 AC: 21053 AN: 41454

American (AMR) AF: 0.802 AC: 12241 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2883 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5151 AN: 5162

South Asian (SAS) AF: 0.899 AC: 4335 AN: 4822

European-Finnish (FIN) AF: 0.851 AC: 9009 AN: 10588

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54841 AN: 67982

Other (OTH) AF: 0.748 AC: 1579 AN: 2110

Alfa AF: 0.776 Hom.: 21696

Bravo AF: 0.721

Asia WGS AF: 0.907 AC: 3153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		0.30
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: rs533123; hg19: chr1-29141155;