The COMT NM_000754.4:c.472G>A (NP_000745.1:p.(Val158Met)) missense variant has previously been reported in somatic cancers (COSMIC; COSV52889256, n = 12 times). Experimental evidence: Variant-specific studies report approximately three- to fourfold lower COMT enzymatic activity for Met158 than Val158, but assay validation and controls are incompletely documented. Based on available guidelines, this variant is considered to be Benign.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.COMT encodes an enzyme that breaks down catecholamine neurotransmitters such as dopamine, epinephrine, and norepinephrine by adding a methyl group. It also helps process catecholamine-based medicines used to treat high blood pressure, asthma, and Parkinson disease, and is produced in both soluble and membrane-bound forms. COMT has no established role in cancer.
The recorded framework is Generic ACMG/AMP 2015 with ClinGen SVI recommendations. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
Met: variant-specific studies report approximately three- to fourfold lower COMT enzymatic activity for Met158 than Val158, but assay validation and controls are incompletely documented.
Met: rapid-cycling bipolar subgroup OR 25.20, 95% CI 1.43–443.62, exceeds the >5.0 threshold and excludes 1.
Met: gnomAD v4.1 grpmax FAF is 0.515321, exceeding the 0.05 BA1 threshold with 1,610,688 observed alleles.
Met: gnomAD v4.1 grpmax FAF is 0.515321, far above the 0.01 generic BS1 threshold in a large population dataset.
Met at supporting: missense REVEL 0.065 meets the BP4 threshold of <=0.29.
Met: the exact variant was observed in VCFS cases primarily explained by 22q11.2 deletion, an alternate molecular basis for the disease.
Benign: BA1 stand-alone benign is met by the gnomAD allele frequency, and no generic pathogenic combination is satisfied by PS4 strong plus PS3 supporting.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 790,010 / 1,610,688 alleles. Recorded AF 0.49048. Recorded homozygote count 197380.
This variant is present in gnomAD v2.1 (AF= 0.459739; MAF= 45.97390%, 128098/278632 alleles, homozygotes = 30461) and has highest observed frequency in the European (Finnish) population (AF= 0.552421; MAF= 55.24214%, 13004/23540 alleles, homozygotes = 3617); grpmax FAF= 0.516002.
Not available in gnomAD-Canada v1.0.
Recorded REVEL score: 0.065. Refer to the recorded PP3/BP4 rationale for interpretation.
5 Benign. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
No standalone functional evidence summary is recorded in evidence_summary.functional.
This variant has previously been reported in somatic cancers (COSMIC; COSV52889256, n = 12 times).
This variant does not lie in a statistically significant hotspot.
ACMG/AMP criteria under Generic ACMG/AMP 2015 with ClinGen SVI recommendations, with the data and sources behind each one.
28 criteria with recorded statuses: 6 met · 7 not met · 11 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
The variant is COMT NM_000754.4:c.472G>A, p.Val158Met, a common functional polymorphism.
PS1 and PM5 cannot be applied without validated pathogenic comparator missense variants.
PM1 is not met because no qualifying COMT hotspot or critical domain without benign variation was documented.
PP2 is not met because the variant is highly prevalent in population data, contradicting the required low benign missense variation context.
BP1 remains not assessed because a primarily truncating COMT disease mechanism was not established by the available evidence.
PS2, PM6, PP1, and BS4 are not assessed because the available evidence does not contain a disease phenotype, proband-parent testing, or an informative family pedigree with genotype-phenotype data.
PS4 is supported by the small rapid-cycling bipolar subgroup case-control comparison in PMID:8886163, with computed continuity-corrected OR 25.20 and 95% CI 1.43-443.62.
BP5 is supported by the presence of the exact variant in VCFS cases primarily explained by 22q11.2 deletion, an alternate molecular basis.
PP4 is not assessed because no case-specific phenotype establishes a single-etiology COMT disorder.
PP5 and BP6 are not met because ClinVar has no exact-variant expert-panel assertion.
The variant is missense, so PP3 and BP4 use REVEL only and do not use SpliceAI or BayesDel.
REVEL 0.065 does not meet PP3 supporting (>=0.644) and meets BP4 supporting (<=0.29).
Population evidence supports a common benign polymorphism: BA1 and BS1 are met, PM2 is not met, and BS2 is not assessed because the case does not define a penetrant COMT disorder meeting the criterion's applicability requirements.
No criteria match.
NM_000754.4:c.472G>A (COMT p.Val158Met) is directly identified in functional literature as the G>A substitution that produces the low-activity COMT Met allele. PMID:10459407 reports that the substitution decreases COMT enzyme activity approximately three- to fourfold and distinguishes the Val allele as high-activity/thermostable from the Met allele as low-activity/thermolabile. PMID:8886163 likewise identifies the same codon 158 substitution and reports a 3- to 4-fold reduction in enzymatic activity for Met/Met versus Val/Val. These concordant, variant-specific biochemical findings support a damaging effect on COMT function. The evidence is assigned supporting rather than stronger PS3 because the available papers do not provide sufficient detail to verify assay validation, reproducibility, controls, or clinical diagnostic laboratory robustness, and PMID:8886163 cites prior functional work rather than measuring enzyme activity itself.
PS3: Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
Generic ACMG/AMP PS4 is met based on Lachman et al. (PMID:8886163), which directly studied COMT158Met (NM_000754.4:c.472G>A; p.Val158Met) in affected VCFS psychiatric subgroups versus Caucasian controls. In the rapid-cycling bipolar-disorder subgroup, all 8 COMT alleles from 7 affected patients were Met, whereas the control Met frequency was 0.402 among 174 chromosomes (approximately 70 Met and 104 non-Met alleles). This is a case-control comparison even though the paper reports a P value rather than an odds ratio. Using the reported frequencies and a 0.5 continuity correction for the zero affected non-Met cell, I computed OR = (8.5 x 104.5)/(0.5 x 70.5) = 25.20, 95% CI 1.43-443.62; the interval excludes 1. The paper reports P = 0.013, but also describes the association as requiring replication. A separate Parkinson disease case-control study (PMID:8941353) found no enrichment (Met allele frequency 0.46 in 139 cases versus 0.52 in 173 controls); from the reported frequencies I computed OR approximately 0.79, 95% CI 0.57-1.08, which does not meet PS4. The positive, disease-subgroup-specific result supports PS4, but the small subgroup and very wide confidence interval require human review.
The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. ... Relative risk (RR) or odds ratio (OR), as obtained from case-control studies, is >5.0 and the confidence interval around the estimate of RR or OR does not include 1.0.
BA1 is met. The governing generic threshold is >=0.05. The filtering allele frequency is the gnomAD v4.1 grpmax FAF of 0.515321, based on a population with 1,610,688 observed alleles overall; the gnomAD v2.1 non-cancer exome grpmax FAF is also 0.51591043. The gnomAD v4.1 highest point estimate is Amish AF 0.663736 from only 910 alleles and is not used for the decision, but the qualifying grpmax FAF remains above 5%. The variant is also recorded as Benign in ClinVar with multiple submitters and no conflicts, so there is no pathogenic-consensus conflict requiring BA1 to be withheld.
Allele frequency is above 5% in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
BS1 is met. The generic default threshold is >=0.01, and the qualifying gnomAD v4.1 filtering grpmax FAF is 0.515321, far above that threshold, with 1,610,688 observed alleles overall. The gnomAD v2.1 non-cancer exome grpmax FAF is similarly high at 0.51591043. The high frequency is not limited to a small isolate: large ancestry groups also show high frequencies, including European non-Finnish AF=0.516409 in gnomAD v4.1 and Finnish AF=0.550217. This is consistent with a common COMT polymorphism rather than an allele causing a fully penetrant rare disorder; ClinVar also reports a benign, non-conflicting consensus.
Allele frequency is greater than expected for the disorder.
The variant is a missense change, so the governing generic path is REVEL only; the SpliceAI result is not used for missense BP4. REVEL is 0.065, which is at or below the generic BP4 supporting threshold of <= 0.29 (ClinGen SVI REVEL calibration, Pejaver et al. 2022, PMID:36413997), supporting BP4 at supporting strength. BayesDel has no established generic ACMG-strength calibration and is not used.
Missense variant -> REVEL only. ... BP4 (supporting): <= 0.29 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
PMID:8886163 reports the exact COMT158Met variant in patients with velo-cardio-facial syndrome, a condition in which 23 of 25 participants had detectable 22q11 deletions and the authors state that VCFS results from deletion of one or more genes on 22q11. Thus the variant was found in cases with an alternate molecular basis for the disease, satisfying generic BP5. The variant was investigated as a possible modifier of psychiatric manifestations, not as the molecular cause of the deletion syndrome. Human review is appropriate because two patients had typical VCFS stigmata without a detected large deletion and the paper's disease-genotype relationship is heterogeneous.
Variant found in a case with an alternate molecular basis for disease.
No VCEP covers COMT, vcep_materials.json contains no domain table, and the case evidence identifies no established COMT mutational hotspot or critical, well-established functional domain without benign variation. Cancer Hotspots returned no result for COMT V158; COSMIC occurrence alone is not sufficient generic PM1 evidence.
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
PM2 is not met. The generic PM2 supporting threshold is <=0.0001, whereas the gnomAD v4.1 all-comers AF is 0.4904798446 and the filtering grpmax FAF is 0.51532097. The gnomAD v2.1 non-cancer exome AF is 0.4599253948 with grpmax FAF=0.51591043. The variant is therefore common in population controls and is not absent or extremely rare.
Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
The required gene-level pattern is not supported: COMT p.Val158Met is a frequent population polymorphism (gnomAD v4.1 AF 0.49048; 790010/1610688 alleles; 197380 homozygotes), and the evidence does not establish COMT as a gene with a low rate of benign missense variation and a common disease-causing missense mechanism.
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
The variant is a missense change, so the governing generic path is REVEL only; SpliceAI is not used for missense PP3/BP4. REVEL is 0.065, which is below the generic PP3 supporting threshold of >= 0.644 (ClinGen SVI REVEL calibration, Pejaver et al. 2022, PMID:36413997), so PP3 is not met. BayesDel has no established generic ACMG-strength calibration and is not evidence for PP3.
Missense variant -> REVEL only. ... PP3 (supporting): >= 0.644 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
The exact ClinVar record is classified Benign without an expert-panel submission. The available assertions are from clinical laboratories or OMIM/literature-only records, and the submission audit reports zero expert-panel submissions. Therefore no exact-variant ClinVar expert-panel Pathogenic or Likely pathogenic classification is available to support PP5.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
No variant-specific functional study in the reviewed evidence shows no damaging effect on COMT protein function or splicing. Instead, the available variant-specific biochemical evidence reports approximately three- to fourfold lower enzymatic activity and reduced thermostability for the Met158 allele compared with Val158. Therefore, the evidence does not satisfy BS3 and is directionally inconsistent with a benign functional effect.
BS3: Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
The exact ClinVar record is Benign, but the submission audit reports zero expert-panel submissions. The available benign assertions are from ordinary laboratory submissions or an OMIM/literature-only record, not an exact-variant ClinVar expert-panel classification. Under the required generic BP6 rule, these records cannot trigger BP6.
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
The variant is COMT p.Val158Met, but the available evidence does not identify a previously established pathogenic variant producing the same amino-acid change. The cited literature describes this allele as a common functional polymorphism, not as a pathogenic comparator. A validated pathogenic same-amino-acid comparator is required before PS1 can be applied.
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change.
No case-level information establishes that NM_000754.4:c.472G>A occurred de novo in a patient with a relevant disease, confirms both maternity and paternity, or documents absence of family history. The available evidence describes a common COMT polymorphism and population or functional studies, not a proband-parent trio or disease phenotype.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
PM3 cannot be assessed because the available evidence does not establish that COMT c.472G>A occurs in an affected proband with a pathogenic COMT variant in trans, and it does not establish a recessive COMT disorder, parental testing, or phase. Population, functional, and general association observations do not substitute for the required allelic phase evidence.
For recessive disorders, detected in trans with a pathogenic variant. ... This requires testing of parents (or offspring) to determine phase.
The case evidence does not provide a validated pathogenic missense comparator at COMT residue 158. The comparator harvest contains zero same-residue candidates, and the available papers describe Val158Met itself rather than a different pathogenic missense change at residue 158.
Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before.
No case-level information documents an assumed de novo occurrence of NM_000754.4:c.472G>A in a patient with a relevant disease. There is also no proband-parent testing evidence showing that the variant was absent from one or both parents, whether or not maternity and paternity were confirmed.
Assumed de novo, but without confirmation of paternity and maternity.
No affected family members, pedigrees, meioses, variant genotypes, or phenotype assessments are documented for NM_000754.4:c.472G>A. The reviewed family analysis in PMID:7304673 concerns inherited COMT activity classes rather than segregation of this variant with a defined disease, so it cannot establish PP1.
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease. ... Note: May be used as stronger evidence with increasing segregation data.
The reviewed literature describes patients with VCFS, psychiatric diagnoses, Parkinson disease, and cognitive phenotypes, but it does not provide an index-patient phenotype for this case that is highly specific for a disease caused by a single genetic etiology attributable to COMT c.472G>A. VCFS is primarily associated with a 22q11.2 deletion, and the COMT polymorphism was studied as a possible modifier; therefore the available cohort phenotypes cannot be used as PP4 for this variant.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
BS2 is not assessed. gnomAD documents 197,380 homozygotes in v4.1 and 30,461 homozygotes in v2.1, but the case provides no specific COMT disorder, inheritance model, expected age of onset, or evidence that full penetrance is expected early in life. Therefore, the presence of homozygotes in a population reference dataset cannot be interpreted under the BS2 requirement without defining the disease and its penetrance.
Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
No affected family members with known NM_000754.4:c.472G>A genotypes are documented, so there is no evaluable non-segregation observation. The available population, functional, and association studies do not establish lack of segregation in an affected family, and the phenocopy caveat cannot be evaluated without family phenotype data.
Lack of segregation in affected members of a family. ... Caveat: The presence of phenocopies for common phenotypes (i.e. cancer, epilepsy) can mimic lack of segregation among affected individuals.
The available case evidence does not establish that disease in COMT is caused primarily by truncating variants. The presence of a common COMT missense polymorphism and functional effects does not by itself demonstrate the gene-level truncating-variant disease mechanism required for BP1.
Missense variant in a gene for which primarily truncating variants are known to cause disease.
BP2 cannot be assessed because the available evidence does not establish either a pathogenic variant in trans in a fully penetrant dominant COMT disorder or a pathogenic variant in cis with COMT c.472G>A. No phase-resolved affected-proband or family observation supports either BP2 pathway.
BP2: Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
PVS1 (ClinGen SVI PVS1 recommendations, PMC6185798, pvs1_generic_framework) applies only to null variant classes — nonsense, frameshift, canonical ±1/2 splice-consensus, translation-initiation-codon loss, and stop-loss variants — each expected to trigger nonsense-mediated decay or otherwise abolish normal protein function. NM_000754.4:c.472G>A in COMT is a missense substitution predicted to produce NP_000745.1:p.(Val158Met). As a result, no null-variant mechanism (nonsense-mediated decay, truncation, or canonical splice disruption) is triggered by this variant class, so PVS1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PVS1 for COMT, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_null_variant_class
PM4 (Richards et al. 2015, PMID:25741868) applies to protein length changes: in-frame insertions/deletions in a non-repetitive region, or stop-loss variants that extend the protein past the reference stop codon. NM_000754.4:c.472G>A in COMT is a missense substitution predicted to produce NP_000745.1:p.(Val158Met). As a result, no change in protein length occurs, so there is nothing for this criterion to evaluate, so PM4's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM4 for COMT, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_stop_loss_or_nonrepeat_indel
BP3 (Richards et al. 2015, PMID:25741868) applies to in-frame insertions/deletions located in a repetitive region without a known function. NM_000754.4:c.472G>A in COMT is a missense substitution predicted to produce NP_000745.1:p.(Val158Met). As a result, the variant does not alter protein length within a repeat region, so there is nothing for this criterion to evaluate, so BP3's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP3 for COMT, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_repeat_region_indel
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_000754.4:c.472G>A in COMT is a missense substitution predicted to produce NP_000745.1:p.(Val158Met). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for COMT, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
Every interpreted variant in COMT, mapped onto the exon structure of NM_000754.4. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| Amish604 / 910 | 0.66203 hom |
| European (Finnish)33769 / 61,374 | 0.559240 hom |
| European (non-Finnish)609120 / 1,179,530 | 0.52157401 hom |
| Middle Eastern3053 / 6,062 | 0.5794 hom |
| Remaining individuals28976 / 62,464 | 0.466885 hom |
| Ashkenazi Jewish13590 / 29,582 | 0.463099 hom |
| South Asian40795 / 91,046 | 0.459343 hom |
| Admixed American24411 / 59,924 | 0.414986 hom |
| African/African American22941 / 74,964 | 0.313598 hom |
| East Asian12751 / 44,832 | 0.281831 hom |
| European (Finnish)13004 / 23,540 | 0.553617 hom |
| European (non-Finnish)66166 / 127,280 | 0.5217083 hom |
| Remaining individuals3417 / 7,150 | 0.48810 hom |
| Ashkenazi Jewish4747 / 10,292 | 0.461097 hom |
| South Asian13437 / 30,548 | 0.442982 hom |
| Admixed American14255 / 35,236 | 0.42896 hom |
| African/African American7693 / 24,742 | 0.311219 hom |
| East Asian5379 / 19,844 | 0.27757 hom |
This variant is present in gnomAD v4.1 (AF= 0.49048; MAF= 49.04798%, 790010/1610688 alleles, homozygotes = 197380) and has highest observed frequency in the Amish population (AF= 0.663736; MAF= 66.37363%, 604/910 alleles, homozygotes = 203); grpmax FAF= 0.515321.
This variant is present in gnomAD v2.1 (AF= 0.459739; MAF= 45.97390%, 128098/278632 alleles, homozygotes = 30461) and has highest observed frequency in the European (Finnish) population (AF= 0.552421; MAF= 55.24214%, 13004/23540 alleles, homozygotes = 3617); grpmax FAF= 0.516002.
Not available in gnomAD-Canada v1.0.
The variant is a missense change, so the governing generic path is REVEL only; the SpliceAI result is not used for missense BP4. REVEL is 0.065, which is at or below the generic BP4 supporting threshold of <= 0.29 (ClinGen SVI REVEL calibration, Pejaver et al. 2022, PMID:36413997), supporting BP4 at supporting strength. BayesDel has no established generic ACMG-strength calibration and is not used.
Missense variant -> REVEL only. ... BP4 (supporting): <= 0.29 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
The variant is a missense change, so the governing generic path is REVEL only; SpliceAI is not used for missense PP3/BP4. REVEL is 0.065, which is below the generic PP3 supporting threshold of >= 0.644 (ClinGen SVI REVEL calibration, Pejaver et al. 2022, PMID:36413997), so PP3 is not met. BayesDel has no established generic ACMG-strength calibration and is not evidence for PP3.
Missense variant -> REVEL only. ... PP3 (supporting): >= 0.644 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_000754.4:c.472G>A in COMT is a missense substitution predicted to produce NP_000745.1:p.(Val158Met). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for COMT, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.065. BayesDel score = -0.258812.
10 paper records listed. 3 cited in the classification.
A single base pair change (G 3 A) in exon 4 of the COMT gene, at position 472 in the long mRNA, and 322 in the short mRNA, results in an amino acid change (Val 3 Met), at codon 158 of MB-COMT and codon 108 of S-COMT, that decreases the activity level of the COMT enzyme 3 to 4 fold (Lachman et al 1996b; Lotta et al 1995).
Location Introduction, paragraph describing the functional COMT polymorphism; Results section on nonhuman primate sequencing; Table 2
Context Global population survey of 1,314 individuals from 30 populations using PCR amplification of the COMT region followed by NlaIII digestion and electrophoresis; sequencing of PCR products from seven nonhuman primates.
We and others have recently established that low activity and heat lability are primarily due to a G+A transition at codon 158 of the gene encoding the membrane-bound form of the enzyme (MB-COMT), which corresponds to codon 108 of the soluble form (S-COMT), leading to a valine+ methionine substitution [Lotta et al., 1995; Lachman et al., 1996].
Location Introduction, paragraph describing the codon 108/158 polymorphism; Results, Table III
Context Association study of 25 patients with velo-cardio-facial syndrome and psychiatric diagnoses, with Caucasian North American controls; COMT genotype determined by PCR-RFLP analysis using NlaIII digestion.
There was no significant difference in the genotype frequencies between the two groups.
Location Results and Discussion, Table 1 and allele/genotype association analysis
Context PCR-RFLP/ARMS genotyping in 139 Caucasian idiopathic Parkinson disease patients and 173 Caucasian controls, with allele and genotype frequencies compared statistically.
Our results show that children with 22q11DS who have the Met allele have higher IQ and achievement scores and perform better on measures of prefrontal cognition, such as the Continuous Performance Task, as compared with those with the Val allele.
Abstract; Results; Table 1; Discussion
The correspondence between basal activity and thermostability suggests moreover that the high- and low-activity alleles are themselves the structural genes for RBC COMT, although genetically determined posttranslational modification of COMT is also a possibility.
Discussion, page 289; Table II
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
This variant is present in gnomAD v4.1 (AF= 0.49048; MAF= 49.04798%, 790010/1610688 alleles, homozygotes = 197380) and has highest observed frequency in the Amish population (AF= 0.663736; MAF= 66.37363%, 604/910 alleles, homozygotes = 203); grpmax FAF= 0.515321.
This variant is present in gnomAD v2.1 (AF= 0.459739; MAF= 45.97390%, 128098/278632 alleles, homozygotes = 30461) and has highest observed frequency in the European (Finnish) population (AF= 0.552421; MAF= 55.24214%, 13004/23540 alleles, homozygotes = 3617); grpmax FAF= 0.516002.
Not available in gnomAD-Canada v1.0.
This variant has been reported in ClinVar as Benign (5 clinical laboratories). (ClinVarID = 17591)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.065. BayesDel score = -0.258812.
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52889256, n = 12 times).
This variant does not lie in a statistically significant hotspot.