rs4680
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000754.4(COMT):c.472G>A(p.Val158Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151946 control chromosomes in the gnomAD Genomes database, including 15493 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.44 ( 15493 hom., cov: 33)
Exomes 𝑓: 0.46 ( 27151 hom. )
Consequence
COMT
NM_000754.4 missense
NM_000754.4 missense
Scores
3
14
Clinical Significance
Conservation
PhyloP100: 0.146
Links
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=6.567385E-5).
BP6
?
Variant 22-19963748-G-A is Benign according to our data. Variant chr22-19963748-G-A is described in ClinVar as [Benign]. Clinvar id is 17591. Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-19963748-G-A is described in Lovd as [Benign].
BA1
?
GnomAd highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COMT | NM_000754.4 | c.472G>A | p.Val158Met | missense_variant | 4/6 | ENST00000361682.11 | |
MIR4761 | NR_039918.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COMT | ENST00000361682.11 | c.472G>A | p.Val158Met | missense_variant | 4/6 | 1 | NM_000754.4 | P2 | |
MIR4761 | ENST00000585066.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes AF: 0.440 AC: 66834AN: 151946Hom.: 15493 Cov.: 33
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GnomAD3 exomes AF: 0.461 AC: 114049AN: 247346Hom.: 27151 AF XY: 0.465 AC XY: 62409AN XY: 134140
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GnomAD4 exome AF: 0.496 AC: 723171AN: 1458624Hom.: 181891 AF XY: 0.495 AC XY: 359427AN XY: 725604
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ClinVar
Significance: Benign
Submissions summary: Benign:6Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, PreventionGenetics | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
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 | - | - - |
CATECHOL-O-METHYLTRANSFERASE POLYMORPHISM Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Jan 01, 2011 | - - |
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
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;T;T;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;M;.;M;.
MutationTaster
Benign
P;P;P;P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;.;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;.;T;T;T
Sift4G
Uncertain
D;D;D;D;D;D;T
Polyphen
B;P;B;B;.;B;.
Vest4
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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