Genetic Variant ENST00000349451.3:c.*1840T>A (chr20-64100639-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000349451.3(OPRL1):c.*1840T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OPRL1
ENST00000349451.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.255

Publications

13 publications found

Variant links:

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]

OPRL1 links:

ENSG00000286999 (HGNC:):

ENSG00000286999 links:

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new If you want to explore the variant's impact on the transcript ENST00000349451.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000349451.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OPRL1	NM_001318854.1		c.*1840T>A	3_prime_UTR	Exon 3 of 3	NP_001305783.1	P41146-2
OPRL1	NM_001318855.1		c.*1840T>A	3_prime_UTR	Exon 3 of 3	NP_001305784.1	Q8IXB0
OPRL1	NM_182647.4	MANE Select	c.*1840T>A	downstream_gene	N/A	NP_872588.1	P41146-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OPRL1	ENST00000349451.3	TSL:1	c.*1840T>A	3_prime_UTR	Exon 6 of 6	ENSP00000336764.3	P41146-1
OPRL1	ENST00000355631.8	TSL:1	c.*1840T>A	3_prime_UTR	Exon 4 of 4	ENSP00000347848.4	P41146-1
OPRL1	ENST00000879252.1		c.*1840T>A	3_prime_UTR	Exon 4 of 4	ENSP00000549311.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.0

(source)

DANN

Benign

0.65

PhyloP100

-0.26

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over