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GeneBe

20-64097919-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_182647.4(OPRL1):c.351G>A(p.Pro117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,613,632 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 64 hom., cov: 33)
Exomes 𝑓: 0.0022 ( 50 hom. )

Consequence

OPRL1
NM_182647.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.10
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-64097919-G-A is Benign according to our data. Variant chr20-64097919-G-A is described in ClinVar as [Benign]. Clinvar id is 777612.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.1 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OPRL1NM_182647.4 linkuse as main transcriptc.351G>A p.Pro117= synonymous_variant 4/5 ENST00000336866.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OPRL1ENST00000336866.7 linkuse as main transcriptc.351G>A p.Pro117= synonymous_variant 4/55 NM_182647.4 P1P41146-1
ENST00000660961.1 linkuse as main transcriptn.3064C>T non_coding_transcript_exon_variant 2/2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0160
AC:
2433
AN:
152184
Hom.:
62
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0532
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00935
Gnomad ASJ
AF:
0.00346
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000588
Gnomad OTH
AF:
0.0139
GnomAD3 exomes
AF:
0.00460
AC:
1153
AN:
250922
Hom.:
26
AF XY:
0.00347
AC XY:
471
AN XY:
135834
show subpopulations
Gnomad AFR exome
AF:
0.0536
Gnomad AMR exome
AF:
0.00361
Gnomad ASJ exome
AF:
0.00458
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000706
Gnomad OTH exome
AF:
0.00408
GnomAD4 exome
AF:
0.00223
AC:
3265
AN:
1461330
Hom.:
50
Cov.:
32
AF XY:
0.00199
AC XY:
1450
AN XY:
726950
show subpopulations
Gnomad4 AFR exome
AF:
0.0558
Gnomad4 AMR exome
AF:
0.00434
Gnomad4 ASJ exome
AF:
0.00367
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000301
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000706
Gnomad4 OTH exome
AF:
0.00465
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0160
AC:
2436
AN:
152302
Hom.:
64
Cov.:
33
AF XY:
0.0151
AC XY:
1124
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.0532
Gnomad4 AMR
AF:
0.00928
Gnomad4 ASJ
AF:
0.00346
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000573
Gnomad4 OTH
AF:
0.0137
Alfa
AF:
0.00872
Hom.:
16
Bravo
AF:
0.0189
Asia WGS
AF:
0.00375
AC:
13
AN:
3478
EpiCase
AF:
0.000763
EpiControl
AF:
0.00113

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
Cadd
Benign
1.0
Dann
Benign
0.75

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61742883; hg19: chr20-62729272; API