20-64098224-C-T

Position:

• chr20-64098224-C-T

Variant summary

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

The NM_182647.4(OPRL1):​c.590-52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,601,752 control chromosomes in the GnomAD database, including 17,189 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 0.14 (1541 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15648 hom.)
• Consequence: OPRL1 NM_182647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

Genes affected

OPRL1 (HGNC:8155): (opioid related nociceptin receptor 1) The protein encoded by this gene is a member of the 7 transmembrane-spanning G protein-coupled receptor family, and functions as a receptor for the endogenous, opioid-related neuropeptide, nociceptin/orphanin FQ. This receptor-ligand system modulates a variety of biological functions and neurobehavior, including stress responses and anxiety behavior, learning and memory, locomotor activity, and inflammatory and immune responses. A promoter region between this gene and the 5'-adjacent RGS19 (regulator of G-protein signaling 19) gene on the opposite strand functions bi-directionally as a core-promoter for both genes, suggesting co-operative transcriptional regulation of these two functionally related genes. Alternatively spliced transcript variants have been described for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Dec 2017]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRL1	NM_182647.4	c.590-52C>T		intron_variant		ENST00000336866.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRL1	ENST00000336866.7	c.590-52C>T		intron_variant		5	NM_182647.4	P1
	ENST00000660961.1	n.2759G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21444 AN: 152084 Hom.: 1540 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0875

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.145 AC: 209855 AN: 1449550 Hom.: 15648 Cov.: 33 AF XY: 0.144 AC XY: 103543 AN XY: 719616

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.0743

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.0825

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.141 AC: 21448 AN: 152202 Hom.: 1541 Cov.: 32 AF XY: 0.139 AC XY: 10330 AN XY: 74420

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0875

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.148

Alfa AF: 0.146 Hom.: 353

Bravo AF: 0.137

Asia WGS AF: 0.109 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.75

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: rs2295448; hg19: chr20-62729577; COSMIC: COSV61091200; COSMIC: COSV61091200;