1-28812576-C-G

Variant names:

• chr1-28812576-C-G
• rs750267952
• NM_000911.4:c.193C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000911.4(OPRD1):​c.193C>G​(p.Leu65Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,418,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OPRD1 NM_000911.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0250
• Publications: 0 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]

ENSG00000305996 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11523825).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000911.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRD1	NM_000911.4	MANE Select	c.193C>G	p.Leu65Val	missense	Exon 1 of 3	NP_000902.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRD1	ENST00000234961.7	TSL:1 MANE Select	c.193C>G	p.Leu65Val	missense	Exon 1 of 3	ENSP00000234961.2	P41143
	ENSG00000305996	ENST00000814652.1		n.92-15347C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000200 AC: 4 AN: 200230 AF XY: 0.0000179

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000292

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1418608 Hom.: 0 Cov.: 36 AF XY: 0.00000284 AC XY: 2 AN XY: 705294

African (AFR) AF: 0.00 AC: 0 AN: 30256

American (AMR) AF: 0.00 AC: 0 AN: 41440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25146

East Asian (EAS) AF: 0.0000555 AC: 2 AN: 36008

South Asian (SAS) AF: 0.00 AC: 0 AN: 82652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097324

Other (OTH) AF: 0.00 AC: 0 AN: 58920

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.00000830 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.025
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.23	N
REVEL	Benign	0.076
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.32		Gain of helix (P = 0.132)
MVP		0.48
MPC		0.76
ClinPred		0.053	T
GERP RS		3.4
PromoterAI		-0.038	Neutral
Varity_R		0.24
gMVP		0.41
Mutation Taster		=47/53	disease causing

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: rs750267952; hg19: chr1-29139088;