rs17275521

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000914.5(OPRM1):​c.291-14489G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,050 control chromosomes in the GnomAD database, including 1,600 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 ( 1600 hom., cov: 32)

Consequence

OPRM1
NM_000914.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.504
Variant links:
Genes affected
OPRM1 (HGNC:8156): (opioid receptor mu 1) This gene encodes one of at least three opioid receptors in humans; the mu opioid receptor (MOR). The MOR is the principal target of endogenous opioid peptides and opioid analgesic agents such as beta-endorphin and enkephalins. The MOR also has an important role in dependence to other drugs of abuse, such as nicotine, cocaine, and alcohol via its modulation of the dopamine system. The NM_001008503.2:c.118A>G allele has been associated with opioid and alcohol addiction and variations in pain sensitivity but evidence for it having a causal role is conflicting. Multiple transcript variants encoding different isoforms have been found for this gene. Though the canonical MOR belongs to the superfamily of 7-transmembrane-spanning G-protein-coupled receptors some isoforms of this gene have only 6 transmembrane domains. [provided by RefSeq, Oct 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OPRM1NM_000914.5 linkuse as main transcriptc.291-14489G>A intron_variant ENST00000330432.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OPRM1ENST00000330432.12 linkuse as main transcriptc.291-14489G>A intron_variant 1 NM_000914.5 P1P35372-1

Frequencies

GnomAD3 genomes
AF:
0.142
AC:
21516
AN:
151934
Hom.:
1600
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.116
Gnomad AMI
AF:
0.236
Gnomad AMR
AF:
0.117
Gnomad ASJ
AF:
0.131
Gnomad EAS
AF:
0.0450
Gnomad SAS
AF:
0.0501
Gnomad FIN
AF:
0.176
Gnomad MID
AF:
0.0918
Gnomad NFE
AF:
0.171
Gnomad OTH
AF:
0.134
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.142
AC:
21521
AN:
152050
Hom.:
1600
Cov.:
32
AF XY:
0.138
AC XY:
10255
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.116
Gnomad4 AMR
AF:
0.117
Gnomad4 ASJ
AF:
0.131
Gnomad4 EAS
AF:
0.0455
Gnomad4 SAS
AF:
0.0502
Gnomad4 FIN
AF:
0.176
Gnomad4 NFE
AF:
0.171
Gnomad4 OTH
AF:
0.131
Alfa
AF:
0.102
Hom.:
190
Bravo
AF:
0.137
Asia WGS
AF:
0.0440
AC:
155
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
0.55
DANN
Benign
0.66

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: rs17275521; hg19: chr6-154396472; API