rs2229205

Variant names:

• chr20-64098078-C-T
• rs2229205
• NM_182647.4:c.510C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_182647.4(OPRL1):​c.510C>T​(p.Val170Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,613,258 control chromosomes in the GnomAD database, including 17,884 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 0.13 (1437 hom., cov: 33)
  • Exomes 𝑓: 0.15 (16447 hom.)
• Consequence: OPRL1 NM_182647.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 27 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]

ENSG00000286999 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=1.59 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRL1	NM_182647.4	c.510C>T	p.Val170Val	synonymous_variant	Exon 4 of 5	ENST00000336866.7	NP_872588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRL1	ENST00000336866.7	c.510C>T	p.Val170Val	synonymous_variant	Exon 4 of 5	5	NM_182647.4	ENSP00000336843.2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20392 AN: 152072 Hom.: 1433 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0927

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.133

GnomAD2 exomes AF: 0.132 AC: 32986 AN: 250262 AF XY: 0.133

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.0833

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.159

Gnomad FIN exome AF: 0.152

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.147 AC: 215311 AN: 1461068 Hom.: 16447 Cov.: 34 AF XY: 0.147 AC XY: 106587 AN XY: 726818

African (AFR) AF: 0.104 AC: 3482 AN: 33480

American (AMR) AF: 0.0866 AC: 3871 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 3365 AN: 26136

East Asian (EAS) AF: 0.143 AC: 5675 AN: 39700

South Asian (SAS) AF: 0.0959 AC: 8274 AN: 86258

European-Finnish (FIN) AF: 0.155 AC: 8151 AN: 52642

Middle Eastern (MID) AF: 0.118 AC: 680 AN: 5768

European-Non Finnish (NFE) AF: 0.156 AC: 173237 AN: 1111980

Other (OTH) AF: 0.142 AC: 8576 AN: 60388

GnomAD4 genome AF: 0.134 AC: 20404 AN: 152190 Hom.: 1437 Cov.: 33 AF XY: 0.134 AC XY: 10006 AN XY: 74400

African (AFR) AF: 0.104 AC: 4308 AN: 41544

American (AMR) AF: 0.110 AC: 1679 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3472

East Asian (EAS) AF: 0.143 AC: 742 AN: 5180

South Asian (SAS) AF: 0.0924 AC: 445 AN: 4818

European-Finnish (FIN) AF: 0.156 AC: 1656 AN: 10594

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.157 AC: 10702 AN: 67972

Other (OTH) AF: 0.134 AC: 282 AN: 2112

Alfa AF: 0.147 Hom.: 5939

Bravo AF: 0.130

Asia WGS AF: 0.104 AC: 364 AN: 3478

EpiCase AF: 0.153

EpiControl AF: 0.153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.60
PhyloP100		1.6
Mutation Taster		=90/10	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: rs2229205; hg19: chr20-62729431; COSMIC: COSV61092192; COSMIC: COSV61092192;