rs6090043

chr20-64086577-C-T

Variant summary

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

The ENST00000349451.3(OPRL1):c.-207C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 197,388 control chromosomes in the GnomAD database, including 23,229 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 0.48 (18019 hom., cov: 33)
  • Exomes 𝑓: 0.47 (5210 hom.)
• Consequence: OPRL1 ENST00000349451.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRL1	NM_182647.4	c.-184-5389C>T		intron_variant		ENST00000336866.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRL1	ENST00000349451.3	c.-207C>T		5_prime_UTR_variant	2/6	1		P1
OPRL1	ENST00000336866.7	c.-184-5389C>T		intron_variant		5	NM_182647.4	P1
OPRL1	ENST00000355631.8	c.-33-6111C>T		intron_variant		1		P1
OPRL1	ENST00000672146.3	c.-184-5389C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73471 AN: 151968 Hom.: 18019 Cov.: 33

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.470 AC: 21304 AN: 45300 Hom.: 5210 Cov.: 0 AF XY: 0.449 AC XY: 11875 AN XY: 26436

Gnomad4 AFR exome AF: 0.458

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.506

Gnomad4 EAS exome AF: 0.650

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.559

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.477

GnomAD4 genome AF: 0.483 AC: 73497 AN: 152088 Hom.: 18019 Cov.: 33 AF XY: 0.488 AC XY: 36267 AN XY: 74336

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.487

Alfa AF: 0.478 Hom.: 19021

Bravo AF: 0.482

Asia WGS AF: 0.458 AC: 1594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	7.2
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: rs6090043; hg19: chr20-62717930;