rs7271530

Variant names:

• chr20-64096562-C-T
• rs7271530
• NM_182647.4:c.234-1240C>T

Variant summary

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

The NM_182647.4(OPRL1):​c.234-1240C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,872 control chromosomes in the GnomAD database, including 18,851 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 0.50 (18851 hom., cov: 32)
• Consequence: OPRL1 NM_182647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• Publications: 20 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRL1	NM_182647.4	c.234-1240C>T		intron_variant	Intron 3 of 4	ENST00000336866.7	NP_872588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRL1	ENST00000336866.7	c.234-1240C>T		intron_variant	Intron 3 of 4	5	NM_182647.4	ENSP00000336843.2
OPRL1	ENST00000349451.3	c.234-1240C>T		intron_variant	Intron 4 of 5	1		ENSP00000336764.3
OPRL1	ENST00000355631.8	c.234-1240C>T		intron_variant	Intron 2 of 3	1		ENSP00000347848.4
OPRL1	ENST00000672146.3	c.234-1240C>T		intron_variant	Intron 3 of 4			ENSP00000500894.2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75218 AN: 151752 Hom.: 18853 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.495 AC: 75242 AN: 151872 Hom.: 18851 Cov.: 32 AF XY: 0.500 AC XY: 37081 AN XY: 74194

African (AFR) AF: 0.488 AC: 20205 AN: 41364

American (AMR) AF: 0.562 AC: 8584 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1662 AN: 3466

East Asian (EAS) AF: 0.585 AC: 3029 AN: 5174

South Asian (SAS) AF: 0.349 AC: 1685 AN: 4824

European-Finnish (FIN) AF: 0.579 AC: 6107 AN: 10542

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32279 AN: 67916

Other (OTH) AF: 0.499 AC: 1054 AN: 2112

Alfa AF: 0.476 Hom.: 12068

Bravo AF: 0.495

Asia WGS AF: 0.469 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.9
DANN	Benign	0.53
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs7271530; hg19: chr20-62727915;