6-154246823-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000337049.8(OPRM1):c.*38C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,372,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 7.3e-7 ( 0 hom. )
Consequence
OPRM1
ENST00000337049.8 3_prime_UTR
ENST00000337049.8 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0880
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]
IPCEF1 (HGNC:21204): (interaction protein for cytohesin exchange factors 1) Predicted to enable peroxidase activity. Predicted to be involved in response to oxidative stress. Predicted to be located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IPCEF1 | NM_001130700.2 | c.77-63G>A | intron_variant | ENST00000367220.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IPCEF1 | ENST00000367220.9 | c.77-63G>A | intron_variant | 2 | NM_001130700.2 | A2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000489 AC: 1AN: 204332Hom.: 0 AF XY: 0.00000905 AC XY: 1AN XY: 110466
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GnomAD4 exome AF: 7.29e-7 AC: 1AN: 1372536Hom.: 0 Cov.: 30 AF XY: 0.00000148 AC XY: 1AN XY: 676388
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GnomAD4 genome Cov.: 31
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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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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at