rs6090043

Variant names:

• chr20-64086577-C-T
• rs6090043
• ENST00000349451.3:c.-207C>T

Variant summary

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

The ENST00000349451.3(OPRL1):​c.-207C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 197,388 control chromosomes in the GnomAD database, including 23,229 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 0.48 (18019 hom., cov: 33)
  • Exomes 𝑓: 0.47 (5210 hom.)
• Consequence: OPRL1 ENST00000349451.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• Publications: 28 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRL1	NM_182647.4	c.-184-5389C>T		intron_variant	Intron 1 of 4	ENST00000336866.7	NP_872588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRL1	ENST00000336866.7	c.-184-5389C>T		intron_variant	Intron 1 of 4	5	NM_182647.4	ENSP00000336843.2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73471 AN: 151968 Hom.: 18019 Cov.: 33

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.470 AC: 21304 AN: 45300 Hom.: 5210 Cov.: 0 AF XY: 0.449 AC XY: 11875 AN XY: 26436

African (AFR) AF: 0.458 AC: 436 AN: 952

American (AMR) AF: 0.609 AC: 4068 AN: 6678

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 2092 AN: 4138

East Asian (EAS) AF: 0.650 AC: 26 AN: 40

South Asian (SAS) AF: 0.331 AC: 3195 AN: 9652

European-Finnish (FIN) AF: 0.559 AC: 1743 AN: 3118

Middle Eastern (MID) AF: 0.461 AC: 117 AN: 254

European-Non Finnish (NFE) AF: 0.470 AC: 8782 AN: 18696

Other (OTH) AF: 0.477 AC: 845 AN: 1772

GnomAD4 genome AF: 0.483 AC: 73497 AN: 152088 Hom.: 18019 Cov.: 33 AF XY: 0.488 AC XY: 36267 AN XY: 74336

African (AFR) AF: 0.453 AC: 18783 AN: 41456

American (AMR) AF: 0.560 AC: 8552 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1667 AN: 3468

East Asian (EAS) AF: 0.583 AC: 3019 AN: 5180

South Asian (SAS) AF: 0.334 AC: 1609 AN: 4816

European-Finnish (FIN) AF: 0.577 AC: 6100 AN: 10572

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.472 AC: 32104 AN: 67998

Other (OTH) AF: 0.487 AC: 1029 AN: 2112

Alfa AF: 0.478 Hom.: 33387

Bravo AF: 0.482

Asia WGS AF: 0.458 AC: 1594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.75
PhyloP100		0.070
Mutation Taster		=100/0	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: rs6090043; hg19: chr20-62717930;