rs2295448

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-64098224-C-G
• chr20-64098224-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000336866.7(OPRL1):​c.590-52C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,449,672 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OPRL1 ENST00000336866.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000336866.7. 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>G		intron	N/A	NP_872588.1
	OPRL1	NM_001318853.2		c.590-52C>G		intron	N/A	NP_001305782.1
	OPRL1	NM_000913.6		c.590-52C>G		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>G		intron	N/A	ENSP00000336843.2
	OPRL1	ENST00000349451.3	TSL:1	c.590-52C>G		intron	N/A	ENSP00000336764.3
	OPRL1	ENST00000355631.8	TSL:1	c.590-52C>G		intron	N/A	ENSP00000347848.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1449672 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 719676

African (AFR) AF: 0.00 AC: 0 AN: 33196

American (AMR) AF: 0.00 AC: 0 AN: 44090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25376

East Asian (EAS) AF: 0.0000759 AC: 3 AN: 39536

South Asian (SAS) AF: 0.00 AC: 0 AN: 84946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104854

Other (OTH) AF: 0.00 AC: 0 AN: 59856

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.89
DANN	Benign	0.60
PhyloP100		-1.3

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;