20-64100639-T-C

Position:

• chr20-64100639-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318854.1(OPRL1):​c.*1840T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 152,350 control chromosomes in the GnomAD database, including 66,641 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 0.94 (66621 hom., cov: 33)
  • Exomes 𝑓: 0.92 (20 hom.)
• Consequence: OPRL1 NM_001318854.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRL1	NM_182647.4	c.*1840T>C		downstream_gene_variant		ENST00000336866.7	NP_872588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRL1	ENST00000336866.7	c.*1840T>C		downstream_gene_variant		5	NM_182647.4	ENSP00000336843.2

Frequencies

GnomAD3 genomes AF: 0.935 AC: 142297 AN: 152184 Hom.: 66569 Cov.: 33

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.955

GnomAD4 exome AF: 0.917 AC: 44 AN: 48 Hom.: 20 Cov.: 0 AF XY: 0.921 AC XY: 35 AN XY: 38

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.900

Gnomad4 OTH exome AF: 0.875

GnomAD4 genome AF: 0.935 AC: 142408 AN: 152302 Hom.: 66621 Cov.: 33 AF XY: 0.939 AC XY: 69898 AN XY: 74474

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.965

Gnomad4 ASJ AF: 0.969

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.952

Gnomad4 FIN AF: 0.942

Gnomad4 NFE AF: 0.915

Gnomad4 OTH AF: 0.956

Alfa AF: 0.926 Hom.: 73779

Bravo AF: 0.937

Asia WGS AF: 0.973 AC: 3385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.68

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: rs6089789; hg19: chr20-62731992;