20-64098224-C-T

Variant names:

• chr20-64098224-C-T
• rs2295448
• NM_182647.4:c.590-52C>T

Variant summary

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

The NM_001318853.2(OPRL1):​c.590-52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,601,752 control chromosomes in the GnomAD database, including 17,189 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 0.14 (1541 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15648 hom.)
• Consequence: OPRL1 NM_001318853.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318853.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRL1	NM_182647.4	MANE Select	c.590-52C>T		intron	N/A	NP_872588.1
	OPRL1	NM_001318853.2		c.590-52C>T		intron	N/A	NP_001305782.1
	OPRL1	NM_000913.6		c.590-52C>T		intron	N/A	NP_000904.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRL1	ENST00000336866.7	TSL:5 MANE Select	c.590-52C>T		intron	N/A	ENSP00000336843.2
	OPRL1	ENST00000349451.3	TSL:1	c.590-52C>T		intron	N/A	ENSP00000336764.3
	OPRL1	ENST00000355631.8	TSL:1	c.590-52C>T		intron	N/A	ENSP00000347848.4

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21444 AN: 152084 Hom.: 1540 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0875

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.145 AC: 209855 AN: 1449550 Hom.: 15648 Cov.: 33 AF XY: 0.144 AC XY: 103543 AN XY: 719616

African (AFR) AF: 0.142 AC: 4721 AN: 33194

American (AMR) AF: 0.0743 AC: 3274 AN: 44084

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 4711 AN: 25368

East Asian (EAS) AF: 0.0825 AC: 3261 AN: 39536

South Asian (SAS) AF: 0.123 AC: 10479 AN: 84934

European-Finnish (FIN) AF: 0.146 AC: 7601 AN: 52086

Middle Eastern (MID) AF: 0.110 AC: 631 AN: 5718

European-Non Finnish (NFE) AF: 0.151 AC: 166498 AN: 1104790

Other (OTH) AF: 0.145 AC: 8679 AN: 59840

GnomAD4 genome AF: 0.141 AC: 21448 AN: 152202 Hom.: 1541 Cov.: 32 AF XY: 0.139 AC XY: 10330 AN XY: 74420

African (AFR) AF: 0.140 AC: 5809 AN: 41514

American (AMR) AF: 0.103 AC: 1570 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 678 AN: 3468

East Asian (EAS) AF: 0.0875 AC: 452 AN: 5168

South Asian (SAS) AF: 0.130 AC: 630 AN: 4828

European-Finnish (FIN) AF: 0.150 AC: 1588 AN: 10604

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10212 AN: 67994

Other (OTH) AF: 0.148 AC: 312 AN: 2114

Alfa AF: 0.146 Hom.: 365

Bravo AF: 0.137

Asia WGS AF: 0.109 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.75
PhyloP100		-1.3
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: rs2295448; hg19: chr20-62729577; COSMIC: COSV61091200; COSMIC: COSV61091200;