rs419335

Variant names:

• chr1-28825332-A-G
• rs419335
• NM_000911.4:c.227+12722A>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.227+12722A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,014 control chromosomes in the GnomAD database, including 17,378 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 0.44 (17378 hom., cov: 32)
• Consequence: OPRD1 NM_000911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 16 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.227+12722A>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.227+12722A>G		intron_variant	Intron 1 of 2	1	NM_000911.4	ENSP00000234961.2
ENSG00000305996	ENST00000814652.1	n.92-2591A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66906 AN: 151896 Hom.: 17351 Cov.: 32

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.441 AC: 66981 AN: 152014 Hom.: 17378 Cov.: 32 AF XY: 0.435 AC XY: 32305 AN XY: 74298

African (AFR) AF: 0.729 AC: 30190 AN: 41430

American (AMR) AF: 0.399 AC: 6083 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1287 AN: 3472

East Asian (EAS) AF: 0.185 AC: 956 AN: 5156

South Asian (SAS) AF: 0.285 AC: 1377 AN: 4824

European-Finnish (FIN) AF: 0.315 AC: 3330 AN: 10572

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22464 AN: 67984

Other (OTH) AF: 0.444 AC: 937 AN: 2112

Alfa AF: 0.442 Hom.: 3278

Bravo AF: 0.466

Asia WGS AF: 0.274 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.9
DANN	Benign	0.40
PhyloP100		0.26
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: rs419335; hg19: chr1-29151844;