chr1-28863085-C-T

Position:

• chr1-28863085-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000911.4(OPRD1):​c.921C>T​(p.Gly307=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,607,094 control chromosomes in the GnomAD database, including 255,002 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 0.51 (21057 hom., cov: 34)
  • Exomes 𝑓: 0.56 (233945 hom.)
• Consequence: OPRD1 NM_000911.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=0.399 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.921C>T	p.Gly307=	synonymous_variant	3/3	ENST00000234961.7	NP_000902.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRD1	ENST00000234961.7	c.921C>T	p.Gly307=	synonymous_variant	3/3	1	NM_000911.4	ENSP00000234961	P1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77752 AN: 152056 Hom.: 21044 Cov.: 34

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.506

GnomAD3 exomes AF: 0.589 AC: 141859 AN: 240868 Hom.: 43180 AF XY: 0.589 AC XY: 77105 AN XY: 130858

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.717

Gnomad ASJ exome AF: 0.467

Gnomad EAS exome AF: 0.768

Gnomad SAS exome AF: 0.694

Gnomad FIN exome AF: 0.572

Gnomad NFE exome AF: 0.543

Gnomad OTH exome AF: 0.565

GnomAD4 exome AF: 0.562 AC: 817470 AN: 1454920 Hom.: 233945 Cov.: 63 AF XY: 0.565 AC XY: 408802 AN XY: 723418

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.710

Gnomad4 ASJ exome AF: 0.468

Gnomad4 EAS exome AF: 0.786

Gnomad4 SAS exome AF: 0.690

Gnomad4 FIN exome AF: 0.570

Gnomad4 NFE exome AF: 0.548

Gnomad4 OTH exome AF: 0.556

GnomAD4 genome AF: 0.511 AC: 77799 AN: 152174 Hom.: 21057 Cov.: 34 AF XY: 0.523 AC XY: 38888 AN XY: 74406

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.772

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.510

Alfa AF: 0.533 Hom.: 6711

Bravo AF: 0.505

Asia WGS AF: 0.687 AC: 2390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	11
DANN	Benign	0.90

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: rs2234918; hg19: chr1-29189597; COSMIC: COSV52384215;