1-28812463-G-T

Position:

• chr1-28812463-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.80G>T​(p.Cys27Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 1,522,638 control chromosomes in the GnomAD database, including 588,833 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.90 (62309 hom., cov: 35)
  • Exomes 𝑓: 0.88 (526524 hom.)
• Consequence: OPRD1 NM_000911.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260

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 (MetaRNN=5.478345E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRD1	NM_000911.4	c.80G>T	p.Cys27Phe	missense_variant	1/3	ENST00000234961.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRD1	ENST00000234961.7	c.80G>T	p.Cys27Phe	missense_variant	1/3	1	NM_000911.4	P1

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137377 AN: 152082 Hom.: 62259 Cov.: 35

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.942

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.917

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.885

GnomAD3 exomes AF: 0.910 AC: 109915 AN: 120806 Hom.: 50151 AF XY: 0.909 AC XY: 61540 AN XY: 67684

Gnomad AFR exome AF: 0.970

Gnomad AMR exome AF: 0.940

Gnomad ASJ exome AF: 0.917

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.940

Gnomad FIN exome AF: 0.877

Gnomad NFE exome AF: 0.868

Gnomad OTH exome AF: 0.896

GnomAD4 exome AF: 0.876 AC: 1200080 AN: 1370444 Hom.: 526524 Cov.: 61 AF XY: 0.877 AC XY: 593827 AN XY: 676960

Gnomad4 AFR exome AF: 0.966

Gnomad4 AMR exome AF: 0.931

Gnomad4 ASJ exome AF: 0.918

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.939

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.861

Gnomad4 OTH exome AF: 0.890

GnomAD4 genome AF: 0.903 AC: 137480 AN: 152194 Hom.: 62309 Cov.: 35 AF XY: 0.904 AC XY: 67279 AN XY: 74394

Gnomad4 AFR AF: 0.961

Gnomad4 AMR AF: 0.900

Gnomad4 ASJ AF: 0.920

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.942

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.884

Alfa AF: 0.875 Hom.: 69781

Bravo AF: 0.906

TwinsUK AF: 0.854 AC: 3168

ALSPAC AF: 0.865 AC: 3332

ESP6500AA AF: 0.970 AC: 3689

ESP6500EA AF: 0.889 AC: 6762

ExAC AF: 0.878 AC: 88436

Asia WGS AF: 0.960 AC: 3332 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.74
DEOGEN2	Benign	0.20	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.25	T;T
MetaRNN	Benign	5.5e-7	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.69	.;N
MutationTaster	Benign	1.0	P
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.87	.;N
REVEL	Benign	0.10
Sift	Benign	0.71	.;T
Sift4G	Benign	0.71	T;T
Polyphen		0.0	.;B
Vest4		0.032
MPC		1.1
ClinPred		0.00014	T
GERP RS		2.9
Varity_R		0.053
gMVP		0.38

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: rs1042114; hg19: chr1-29138975; COSMIC: COSV52379995;