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GeneBe

rs4633

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000754.4(COMT):c.186C>T(p.His62=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152012 control chromosomes in the gnomAD Genomes database, including 15738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15738 hom., cov: 34)
Exomes 𝑓: 0.46 ( 27712 hom. )

Consequence

COMT
NM_000754.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -1.83

Links

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
?
Variant 22-19962712-C-T is Benign according to our data. Variant chr22-19962712-C-T is described in ClinVar as [Benign]. Clinvar id is 256785. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-19962712-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.83 with no splicing effect.
BA1
?
GnomAd highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COMTNM_000754.4 linkuse as main transcriptc.186C>T p.His62= synonymous_variant 3/6 ENST00000361682.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COMTENST00000361682.11 linkuse as main transcriptc.186C>T p.His62= synonymous_variant 3/61 NM_000754.4 P2P21964-1

Frequencies

GnomAD3 genomes
AF:
0.446
AC:
67786
AN:
152012
Hom.:
15738
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.331
Gnomad AMI
AF:
0.664
Gnomad AMR
AF:
0.405
Gnomad ASJ
AF:
0.460
Gnomad EAS
AF:
0.269
Gnomad SAS
AF:
0.457
Gnomad FIN
AF:
0.551
Gnomad MID
AF:
0.465
Gnomad NFE
AF:
0.518
Gnomad OTH
AF:
0.425
GnomAD3 exomes
AF:
0.463
AC:
115901
AN:
250082
Hom.:
27712
AF XY:
0.467
AC XY:
63276
AN XY:
135450
show subpopulations
Gnomad AFR exome
AF:
0.332
Gnomad AMR exome
AF:
0.405
Gnomad ASJ exome
AF:
0.470
Gnomad EAS exome
AF:
0.269
Gnomad SAS exome
AF:
0.449
Gnomad FIN exome
AF:
0.545
Gnomad NFE exome
AF:
0.519
Gnomad OTH exome
AF:
0.475
GnomAD4 exome
AF:
0.497
AC:
726681
AN:
1461162
Hom.:
183159
AF XY:
0.497
AC XY:
361149
AN XY:
726878
show subpopulations
Gnomad4 AFR exome
AF:
0.328
Gnomad4 AMR exome
AF:
0.409
Gnomad4 ASJ exome
AF:
0.470
Gnomad4 EAS exome
AF:
0.279
Gnomad4 SAS exome
AF:
0.457
Gnomad4 FIN exome
AF:
0.546
Gnomad4 NFE exome
AF:
0.517
Gnomad4 OTH exome
AF:
0.468
Alfa
AF:
0.489
Hom.:
22635
Bravo
AF:
0.427
Asia WGS
AF:
0.347
AC:
1206
AN:
3478
EpiCase
AF:
0.499
EpiControl
AF:
0.504

ClinVar

Significance: Benign
Submissions summary: Benign:6Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:5
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, Part of Exact Sciences-- -
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, Amsterdam University Medical Center-- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021This variant is associated with the following publications: (PMID: 21486747) -
Tramadol response Other:1
drug response, no assertion criteria providedresearchBruce Budowle Laboratory, University of North Texas Health Science CenterApr 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
Cadd
Benign
0.46
Dann
Benign
0.92
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4633; hg19: chr22-19950235; COSMIC: COSV52889434; COSMIC: COSV52889434; API