chr1-28835953-G-A

Position:

• chr1-28835953-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000911.4(OPRD1):​c.228-23001G>A 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 152,034 control chromosomes in the GnomAD database, including 10,146 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 (10146 hom., cov: 31)
• Consequence: OPRD1 NM_000911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.228-23001G>A		intron_variant		ENST00000234961.7	NP_000902.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRD1	ENST00000234961.7	c.228-23001G>A		intron_variant		1	NM_000911.4	ENSP00000234961	P1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54520 AN: 151916 Hom.: 10133 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.359 AC: 54573 AN: 152034 Hom.: 10146 Cov.: 31 AF XY: 0.356 AC XY: 26440 AN XY: 74318

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.388

Alfa AF: 0.356 Hom.: 1647

Bravo AF: 0.372

Asia WGS AF: 0.259 AC: 898 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	0.67
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs760589; hg19: chr1-29162465; COSMIC: COSV52382897;