rs17174629

Variant summary

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

The NM_001145279.4(OPRM1):​c.1-935A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 152,246 control chromosomes in the GnomAD database, including 210 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 0.030 ( 210 hom., cov: 32)

Consequence

OPRM1
NM_001145279.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.443
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]

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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 (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OPRM1NM_001145279.4 linkuse as main transcriptc.1-935A>G intron_variant NP_001138751.1 P35372-10B8K2Q5
OPRM1NM_001145281.3 linkuse as main transcriptc.47+27667A>G intron_variant NP_001138753.1 P35372-13B8K2Q5
OPRM1NM_001145280.4 linkuse as main transcriptc.-11+27208A>G intron_variant NP_001138752.1 P35372-12B8K2Q5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OPRM1ENST00000434900.6 linkuse as main transcriptc.1-935A>G intron_variant 1 ENSP00000394624.2 P35372-10
OPRM1ENST00000518759.5 linkuse as main transcriptc.47+27667A>G intron_variant 1 ENSP00000430260.1 P35372-13
OPRM1ENST00000520708.5 linkuse as main transcriptc.-11+27208A>G intron_variant 1 ENSP00000430876.1 P35372-12
OPRM1ENST00000520282.5 linkuse as main transcriptc.11-1185A>G intron_variant 1 ENSP00000430247.1 E7EW71

Frequencies

GnomAD3 genomes
AF:
0.0296
AC:
4509
AN:
152128
Hom.:
209
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.103
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0116
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000827
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000426
Gnomad OTH
AF:
0.0167
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0297
AC:
4528
AN:
152246
Hom.:
210
Cov.:
32
AF XY:
0.0286
AC XY:
2132
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.103
Gnomad4 AMR
AF:
0.0116
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000828
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000426
Gnomad4 OTH
AF:
0.0184
Alfa
AF:
0.0259
Hom.:
19
Bravo
AF:
0.0334
Asia WGS
AF:
0.0110
AC:
37
AN:
3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.70
DANN
Benign
0.53

Splicing

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: rs17174629; hg19: chr6-154359361; API