rs6090041

Variant names:

• chr20-64081323-G-A
• rs6090041
• NM_182647.4:c.-185+971G>A

Variant summary

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

The NM_182647.4(OPRL1):​c.-185+971G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,156 control chromosomes in the GnomAD database, including 33,311 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 0.65 (33311 hom., cov: 34)
• Consequence: OPRL1 NM_182647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 25 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182647.4. 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.-185+971G>A		intron	N/A	NP_872588.1	P41146-1
	OPRL1	NM_001318853.2		c.-185+971G>A		intron	N/A	NP_001305782.1	A0A5F9ZI64
	OPRL1	NM_000913.6		c.-34+971G>A		intron	N/A	NP_000904.1	P41146-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRL1	ENST00000336866.7	TSL:5 MANE Select	c.-185+971G>A		intron	N/A	ENSP00000336843.2	P41146-1
	OPRL1	ENST00000355631.8	TSL:1	c.-34+971G>A		intron	N/A	ENSP00000347848.4	P41146-1
	OPRL1	ENST00000672146.3		c.-185+971G>A		intron	N/A	ENSP00000500894.2	A0A5F9ZI64

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98795 AN: 152038 Hom.: 33308 Cov.: 34

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.650 AC: 98829 AN: 152156 Hom.: 33311 Cov.: 34 AF XY: 0.658 AC XY: 48944 AN XY: 74388

African (AFR) AF: 0.467 AC: 19357 AN: 41486

American (AMR) AF: 0.764 AC: 11685 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2232 AN: 3472

East Asian (EAS) AF: 0.922 AC: 4774 AN: 5180

South Asian (SAS) AF: 0.591 AC: 2855 AN: 4830

European-Finnish (FIN) AF: 0.773 AC: 8198 AN: 10606

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47537 AN: 67966

Other (OTH) AF: 0.668 AC: 1410 AN: 2112

Alfa AF: 0.683 Hom.: 77160

Bravo AF: 0.642

Asia WGS AF: 0.730 AC: 2537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.2
DANN	Benign	0.85
PhyloP100		0.062
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6090041; hg19: chr20-62712676;