rs4654327

Positions:

• chr1-28863626-G-A
• chr1-28863626-G-T

Variant summary

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

The NM_000911.4(OPRD1):​c.*343G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 272,194 control chromosomes in the GnomAD database, including 37,291 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 (18981 hom., cov: 33)
  • Exomes 𝑓: 0.54 (18310 hom.)
• Consequence: OPRD1 NM_000911.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRD1	NM_000911.4	c.*343G>A		3_prime_UTR_variant	3/3	ENST00000234961.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRD1	ENST00000234961.7	c.*343G>A		3_prime_UTR_variant	3/3	1	NM_000911.4	P1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73495 AN: 151980 Hom.: 18974 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.541 AC: 64940 AN: 120094 Hom.: 18310 Cov.: 0 AF XY: 0.541 AC XY: 32673 AN XY: 60418

Gnomad4 AFR exome AF: 0.310

Gnomad4 AMR exome AF: 0.594

Gnomad4 ASJ exome AF: 0.432

Gnomad4 EAS exome AF: 0.818

Gnomad4 SAS exome AF: 0.702

Gnomad4 FIN exome AF: 0.592

Gnomad4 NFE exome AF: 0.514

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome AF: 0.483 AC: 73531 AN: 152100 Hom.: 18981 Cov.: 33 AF XY: 0.497 AC XY: 36953 AN XY: 74380

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.463

Alfa AF: 0.503 Hom.: 19809

Bravo AF: 0.470

Asia WGS AF: 0.684 AC: 2379 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	0.11
DANN	Benign	0.71

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: rs4654327; hg19: chr1-29190138;