rs4818
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000754(COMT):c.408C>G(p.Leu136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151960 control chromosomes in the gnomAD Genomes database, including 8492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (β β ).
Frequency
Genomes: π 0.32 ( 8492 hom., cov: 33)
Exomes π: 0.34 ( 14967 hom. )
Consequence
COMT
NM_000754 synonymous
NM_000754 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.271
Links
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 22:19963684-C>G is Benign according to our data. Variant chr22-19963684-C-G is described in ClinVar as [Benign]. Clinvar id is 256786. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-19963684-C-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.271 with no splicing effect.
BA1
?
GnomAd highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COMT | NM_000754.4 | c.408C>G | p.Leu136= | synonymous_variant | 4/6 | ENST00000361682.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COMT | ENST00000361682.11 | c.408C>G | p.Leu136= | synonymous_variant | 4/6 | 1 | NM_000754.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.324 AC: 49164AN: 151960Hom.: 8492 Cov.: 33
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GnomAD3 exomes AF: 0.338 AC: 84214AN: 249446Hom.: 14967 AF XY: 0.346 AC XY: 46860AN XY: 135238
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GnomAD4 exome AF: 0.380 AC: 555409AN: 1460394Hom.: 107780 AF XY: 0.380 AC XY: 276355AN XY: 726524
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ClinVar
Significance: Benign
Submissions summary: Benign:6Other:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, PreventionGenetics | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | This variant is associated with the following publications: (PMID: 19641441, 9323320, 30218069, 25766270) - |
methamphetamine use disorder Other:1
Uncertain risk allele, no assertion criteria provided | case-control | Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology | Jan 16, 2023 | - - |
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
Source:
Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Find out SpliceAI and Pangolin per-transcript scores at