Variant chr20-64092763-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182647.4(OPRL1):c.43G>A(p.Gly15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,460,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

OPRL1
NM_182647.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.865

Variant links:

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]

OPRL1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04813999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRL1	NM_182647.4 linkuse as main transcript	c.43G>A	p.Gly15Ser	missense_variant	3/5	ENST00000336866.7	NP_872588.1	P41146-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OPRL1	ENST00000336866.7 linkuse as main transcript	c.43G>A	p.Gly15Ser	missense_variant	3/5	5	NM_182647.4	ENSP00000336843.2	P41146-1
OPRL1	ENST00000349451.3 linkuse as main transcript	c.43G>A	p.Gly15Ser	missense_variant	4/6	1		ENSP00000336764.3	P41146-1
OPRL1	ENST00000355631.8 linkuse as main transcript	c.43G>A	p.Gly15Ser	missense_variant	2/4	1		ENSP00000347848.4	P41146-1
OPRL1	ENST00000672146.3 linkuse as main transcript	c.43G>A	p.Gly15Ser	missense_variant	3/5			ENSP00000500894.2	A0A5F9ZI64

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249824

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135614

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1460428

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726490

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000827

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.43G>A (p.G15S) alteration is located in exon 3 (coding exon 1) of the OPRL1 gene. This alteration results from a G to A substitution at nucleotide position 43, causing the glycine (G) at amino acid position 15 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.048

DANN

Benign

0.80

DEOGEN2

Benign

0.088

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.60

.;.;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.048

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

0.37

N;N;N

REVEL

Benign

0.062

Sift

Benign

0.44

T;T;T

Sift4G

Benign

0.42

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.072

MVP

0.31

MPC

0.53

ClinPred

0.027

GERP RS

0.44

Varity_R

0.036

gMVP

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over