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GeneBe

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: 𝑓 0.32 ( 8492 hom., cov: 33)
Exomes 𝑓: 0.34 ( 14967 hom. )

Consequence

COMT
NM_000754 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:2

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
COMTNM_000754.4 linkuse as main transcriptc.408C>G p.Leu136= synonymous_variant 4/6 ENST00000361682.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COMTENST00000361682.11 linkuse as main transcriptc.408C>G p.Leu136= synonymous_variant 4/61 NM_000754.4 P2P21964-1

Frequencies

GnomAD3 genomes
AF:
0.324
AC:
49164
AN:
151960
Hom.:
8492
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.206
Gnomad AMI
AF:
0.306
Gnomad AMR
AF:
0.304
Gnomad ASJ
AF:
0.471
Gnomad EAS
AF:
0.325
Gnomad SAS
AF:
0.311
Gnomad FIN
AF:
0.301
Gnomad MID
AF:
0.424
Gnomad NFE
AF:
0.395
Gnomad OTH
AF:
0.359
GnomAD3 exomes
AF:
0.338
AC:
84214
AN:
249446
Hom.:
14967
AF XY:
0.346
AC XY:
46860
AN XY:
135238
show subpopulations
Gnomad AFR exome
AF:
0.197
Gnomad AMR exome
AF:
0.213
Gnomad ASJ exome
AF:
0.460
Gnomad EAS exome
AF:
0.323
Gnomad SAS exome
AF:
0.321
Gnomad FIN exome
AF:
0.309
Gnomad NFE exome
AF:
0.395
Gnomad OTH exome
AF:
0.370
GnomAD4 exome
AF:
0.380
AC:
555409
AN:
1460394
Hom.:
107780
AF XY:
0.380
AC XY:
276355
AN XY:
726524
show subpopulations
Gnomad4 AFR exome
AF:
0.197
Gnomad4 AMR exome
AF:
0.222
Gnomad4 ASJ exome
AF:
0.460
Gnomad4 EAS exome
AF:
0.309
Gnomad4 SAS exome
AF:
0.320
Gnomad4 FIN exome
AF:
0.314
Gnomad4 NFE exome
AF:
0.401
Gnomad4 OTH exome
AF:
0.377
Alfa
AF:
0.375
Hom.:
3482
Bravo
AF:
0.317
Asia WGS
AF:
0.311
AC:
1081
AN:
3478
EpiCase
AF:
0.416
EpiControl
AF:
0.409

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 submitterclinical testingPreventionGenetics, PreventionGenetics-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, Amsterdam University Medical Center-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021This variant is associated with the following publications: (PMID: 19641441, 9323320, 30218069, 25766270) -
methamphetamine use disorder Other:1
Uncertain risk allele, no assertion criteria providedcase-controlBeijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and ToxicologyJan 16, 2023- -
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
-0.78
Cadd
Benign
5.3
Dann
Benign
0.62
RBP_binding_hub_radar
1.0
RBP_regulation_power_radar
3.2

Splicing

Find out SpliceAI 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: rs4818; hg19: chr22-19951207; COSMIC: COSV52889002; COSMIC: COSV52889002;