chr20-64088023-T-C

Position:

• chr20-64088023-T-C

Variant summary

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

The NM_182647.4(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_182647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRL1	NM_182647.4	c.-184-3943T>C		intron_variant		ENST00000336866.7	NP_872588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRL1	ENST00000336866.7	c.-184-3943T>C		intron_variant		5	NM_182647.4	ENSP00000336843.2
OPRL1	ENST00000349451.3	c.-185+1424T>C		intron_variant		1		ENSP00000336764.3
OPRL1	ENST00000355631.8	c.-33-4665T>C		intron_variant		1		ENSP00000347848.4
OPRL1	ENST00000672146.3	c.-184-3943T>C		intron_variant				ENSP00000500894.2

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

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.965

Gnomad4 ASJ AF: 0.970

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.916

Gnomad4 OTH AF: 0.950

Alfa AF: 0.928 Hom.: 8139

Bravo AF: 0.930

Asia WGS AF: 0.971 AC: 3378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.9
DANN	Benign	0.84

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: rs6010718; hg19: chr20-62719376;