chr1-28848434-A-C

Variant names:

• chr1-28848434-A-C
• rs529520
• NM_000911.4:c.228-10520A>C

Variant summary

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

The NM_000911.4(OPRD1):​c.228-10520A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,960 control chromosomes in the GnomAD database, including 18,765 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 0.48 (18765 hom., cov: 31)
• Consequence: OPRD1 NM_000911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 31 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.228-10520A>C		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.228-10520A>C		intron_variant	Intron 1 of 2	1	NM_000911.4	ENSP00000234961.2

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72178 AN: 151842 Hom.: 18758 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.475 AC: 72219 AN: 151960 Hom.: 18765 Cov.: 31 AF XY: 0.481 AC XY: 35755 AN XY: 74264

African (AFR) AF: 0.271 AC: 11217 AN: 41420

American (AMR) AF: 0.506 AC: 7724 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1914 AN: 3472

East Asian (EAS) AF: 0.871 AC: 4505 AN: 5174

South Asian (SAS) AF: 0.665 AC: 3198 AN: 4812

European-Finnish (FIN) AF: 0.562 AC: 5930 AN: 10550

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36145 AN: 67960

Other (OTH) AF: 0.454 AC: 956 AN: 2108

Alfa AF: 0.508 Hom.: 60084

Bravo AF: 0.458

Asia WGS AF: 0.709 AC: 2466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.65
PhyloP100		-0.10
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: rs529520; hg19: chr1-29174946; COSMIC: COSV52381041;