NM_000911.4:c.59C>A

Variant names:

• chr1-28812442-C-A
• rs778538430
• NM_000911.4:c.59C>A

Variant summary

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

The NM_000911.4(OPRD1):​c.59C>A​(p.Ser20*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000742 in 1,347,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: OPRD1 NM_000911.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.48
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.59C>A	p.Ser20*	stop_gained	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.59C>A	p.Ser20*	stop_gained	Exon 1 of 3	ENSP00000234961.2	P41143
	ENSG00000305996	ENST00000814652.1		n.92-15481C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.42e-7 AC: 1 AN: 1347936 Hom.: 0 Cov.: 29 AF XY: 0.00000150 AC XY: 1 AN XY: 664650

African (AFR) AF: 0.00 AC: 0 AN: 27414

American (AMR) AF: 0.00 AC: 0 AN: 31218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23932

East Asian (EAS) AF: 0.00 AC: 0 AN: 30858

South Asian (SAS) AF: 0.0000133 AC: 1 AN: 75436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4372

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063568

Other (OTH) AF: 0.00 AC: 0 AN: 56190

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	43
DANN	Uncertain	0.99
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.21	N
PhyloP100		3.5
Vest4		0.63
GERP RS		3.4
PromoterAI		0.015	Neutral
Mutation Taster		=51/149	disease causing (fs/PTC)

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: rs778538430; hg19: chr1-29138954;