chr1-28813244-G-A

Variant names:

• chr1-28813244-G-A
• rs2236861
• NM_000911.4:c.227+634G>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+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
• Publications: 32 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=-0.9).
• 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 rank	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.227+634G>A		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+634G>A		intron_variant	Intron 1 of 2	1	NM_000911.4	ENSP00000234961.2
ENSG00000305996	ENST00000814652.1	n.92-14679G>A		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.0828 AC: 3440 AN: 41530

American (AMR) AF: 0.195 AC: 2987 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3470

East Asian (EAS) AF: 0.105 AC: 543 AN: 5182

South Asian (SAS) AF: 0.159 AC: 767 AN: 4826

European-Finnish (FIN) AF: 0.308 AC: 3255 AN: 10566

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16271 AN: 67984

Other (OTH) AF: 0.209 AC: 442 AN: 2114

Alfa AF: 0.218 Hom.: 14649

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
PhyloP100		-1.9
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: rs2236861; hg19: chr1-29139756;