chr6-154246729-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
The ENST00000337049.8(OPRM1):c.1201C>T(p.Arg401Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,613,866 control chromosomes in the GnomAD database, including 3,808 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 0.048 ( 253 hom., cov: 31)
Exomes 𝑓: 0.066 ( 3555 hom. )
Consequence
OPRM1
ENST00000337049.8 stop_gained
ENST00000337049.8 stop_gained
Scores
1
6
Clinical Significance
Conservation
PhyloP100: -5.05
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 Benign. Variant got -8 ACMG points.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IPCEF1 | NM_001130700.2 | c.108G>A | p.Ser36= | synonymous_variant | 5/12 | ENST00000367220.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IPCEF1 | ENST00000367220.9 | c.108G>A | p.Ser36= | synonymous_variant | 5/12 | 2 | NM_001130700.2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0479 AC: 7281AN: 152046Hom.: 253 Cov.: 31
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GnomAD3 exomes AF: 0.0521 AC: 13097AN: 251166Hom.: 475 AF XY: 0.0551 AC XY: 7483AN XY: 135750
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GnomAD4 exome AF: 0.0661 AC: 96671AN: 1461702Hom.: 3555 Cov.: 32 AF XY: 0.0661 AC XY: 48081AN XY: 727160
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GnomAD4 genome AF: 0.0478 AC: 7277AN: 152164Hom.: 253 Cov.: 31 AF XY: 0.0453 AC XY: 3368AN XY: 74378
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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
Calibrated prediction
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BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
D;D;D;D;D
Vest4
GERP RS
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