1-28843081-A-G

Variant names:

• chr1-28843081-A-G
• rs421300
• NM_000911.4:c.228-15873A>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.228-15873A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,668 control chromosomes in the GnomAD database, including 11,512 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 0.38 (11512 hom., cov: 30)
• Consequence: OPRD1 NM_000911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.733
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.228-15873A>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.228-15873A>G		intron_variant	Intron 1 of 2	1	NM_000911.4	ENSP00000234961.2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57369 AN: 151550 Hom.: 11508 Cov.: 30

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.379 AC: 57413 AN: 151668 Hom.: 11512 Cov.: 30 AF XY: 0.375 AC XY: 27814 AN XY: 74084

African (AFR) AF: 0.509 AC: 21032 AN: 41314

American (AMR) AF: 0.379 AC: 5776 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1250 AN: 3470

East Asian (EAS) AF: 0.188 AC: 972 AN: 5170

South Asian (SAS) AF: 0.282 AC: 1357 AN: 4804

European-Finnish (FIN) AF: 0.316 AC: 3306 AN: 10472

Middle Eastern (MID) AF: 0.472 AC: 137 AN: 290

European-Non Finnish (NFE) AF: 0.332 AC: 22532 AN: 67910

Other (OTH) AF: 0.399 AC: 837 AN: 2100

Alfa AF: 0.366 Hom.: 1311

Bravo AF: 0.393

Asia WGS AF: 0.265 AC: 920 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	0.22
DANN	Benign	0.69
PhyloP100		-0.73
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: rs421300; hg19: chr1-29169593;