20-64088023-T-C

Variant names:

• chr20-64088023-T-C
• rs6010718
• NM_182647.4:c.-184-3943T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318853.2(OPRL1):​c.-184-3943T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 152,344 control chromosomes in the GnomAD database, including 65,790 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 0.93 (65790 hom., cov: 36)
• Consequence: OPRL1 NM_001318853.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318853.2. 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
	OPRL1	NM_182647.4	MANE Select	c.-184-3943T>C		intron	N/A	NP_872588.1
	OPRL1	NM_001318853.2		c.-184-3943T>C		intron	N/A	NP_001305782.1
	OPRL1	NM_000913.6		c.-33-4665T>C		intron	N/A	NP_000904.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRL1	ENST00000336866.7	TSL:5 MANE Select	c.-184-3943T>C		intron	N/A	ENSP00000336843.2
	OPRL1	ENST00000349451.3	TSL:1	c.-185+1424T>C		intron	N/A	ENSP00000336764.3
	OPRL1	ENST00000355631.8	TSL:1	c.-33-4665T>C		intron	N/A	ENSP00000347848.4

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141417 AN: 152226 Hom.: 65738 Cov.: 36

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.950

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.929 AC: 141528 AN: 152344 Hom.: 65790 Cov.: 36 AF XY: 0.933 AC XY: 69529 AN XY: 74496

African (AFR) AF: 0.917 AC: 38130 AN: 41580

American (AMR) AF: 0.965 AC: 14769 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3367 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5186

South Asian (SAS) AF: 0.953 AC: 4601 AN: 4830

European-Finnish (FIN) AF: 0.943 AC: 10016 AN: 10624

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.916 AC: 62290 AN: 68024

Other (OTH) AF: 0.950 AC: 2007 AN: 2112

Alfa AF: 0.928 Hom.: 8464

Bravo AF: 0.930

Asia WGS AF: 0.971 AC: 3378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.9
DANN	Benign	0.84
PhyloP100		-0.039
Mutation Taster		=100/0	polymorphism (auto)

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: rs6010718; hg19: chr20-62719376;