rs606545
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000452687.6(OPRM1):c.*19G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,457,050 control chromosomes in the GnomAD database, including 37,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).
Frequency
Genomes: 𝑓 0.21 ( 3500 hom., cov: 30)
Exomes 𝑓: 0.22 ( 34254 hom. )
Consequence
OPRM1
ENST00000452687.6 3_prime_UTR
ENST00000452687.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.715
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=-0.9).
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OPRM1 | NM_000914.5 | c.1165-8253G>A | intron_variant | ENST00000330432.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPRM1 | ENST00000330432.12 | c.1165-8253G>A | intron_variant | 1 | NM_000914.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.207 AC: 31475AN: 151876Hom.: 3497 Cov.: 30
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GnomAD3 exomes AF: 0.195 AC: 29701AN: 152462Hom.: 3191 AF XY: 0.196 AC XY: 15859AN XY: 80952
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GnomAD4 exome AF: 0.224 AC: 292139AN: 1305056Hom.: 34254 Cov.: 21 AF XY: 0.223 AC XY: 144950AN XY: 648652
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GnomAD4 genome ? AF: 0.207 AC: 31508AN: 151994Hom.: 3500 Cov.: 30 AF XY: 0.202 AC XY: 14983AN XY: 74270
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ClinVar
Significance: drug response
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Tramadol response Other:1
drug response, no assertion criteria provided | research | Bruce Budowle Laboratory, University of North Texas Health Science Center | Apr 28, 2018 | - T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1 |
Computational scores
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Name
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at