1-28836056-A-G

Variant names:

• chr1-28836056-A-G
• rs760588
• NM_000911.4:c.228-22898A>G

Variant summary

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

The NM_000911.4(OPRD1):​c.228-22898A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,032 control chromosomes in the GnomAD database, including 10,143 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 0.36 (10143 hom., cov: 31)
• Consequence: OPRD1 NM_000911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.228-22898A>G		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.228-22898A>G		intron_variant	Intron 1 of 2	1	NM_000911.4	ENSP00000234961.2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54539 AN: 151916 Hom.: 10130 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.359 AC: 54591 AN: 152032 Hom.: 10143 Cov.: 31 AF XY: 0.356 AC XY: 26457 AN XY: 74334

African (AFR) AF: 0.447 AC: 18509 AN: 41446

American (AMR) AF: 0.369 AC: 5625 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1287 AN: 3468

East Asian (EAS) AF: 0.181 AC: 937 AN: 5176

South Asian (SAS) AF: 0.284 AC: 1369 AN: 4824

European-Finnish (FIN) AF: 0.316 AC: 3340 AN: 10580

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.329 AC: 22357 AN: 67964

Other (OTH) AF: 0.387 AC: 817 AN: 2110

Alfa AF: 0.338 Hom.: 15875

Bravo AF: 0.372

Asia WGS AF: 0.258 AC: 897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.31
DANN	Benign	0.63
PhyloP100		-2.3
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: rs760588; hg19: chr1-29162568;