chr20-64092869-T-A

Position:

• chr20-64092869-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182647.4(OPRL1):​c.149T>A​(p.Leu50His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OPRL1 NM_182647.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25087652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRL1	NM_182647.4	c.149T>A	p.Leu50His	missense_variant	3/5	ENST00000336866.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRL1	ENST00000336866.7	c.149T>A	p.Leu50His	missense_variant	3/5	5	NM_182647.4	P1
OPRL1	ENST00000349451.3	c.149T>A	p.Leu50His	missense_variant	4/6	1		P1
OPRL1	ENST00000355631.8	c.149T>A	p.Leu50His	missense_variant	2/4	1		P1
OPRL1	ENST00000672146.3	c.149T>A	p.Leu50His	missense_variant	3/5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.24	T;T;T
Eigen	Benign	-0.043
Eigen_PC	Benign	0.018
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	.;.;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.84	L;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.37	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.96	D;D;D
Vest4		0.22
MutPred		0.50		Loss of ubiquitination at K51 (P = 0.0573);Loss of ubiquitination at K51 (P = 0.0573);Loss of ubiquitination at K51 (P = 0.0573);
MVP		0.35
MPC		1.4
ClinPred		0.78	D
GERP RS		3.9
Varity_R		0.33
gMVP		0.49

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: rs1978365576; hg19: chr20-62724222;