chr22-19962712-C-T

Position:

chr22-19962712-C-T

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 0.492 in 1,613,292 control chromosomes in the GnomAD database, including 198,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15737 hom., cov: 34)

Exomes 𝑓: 0.50 ( 183159 hom. )

Consequence

COMT
NM_000754.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -1.83

Variant links:

Genes affected

COMT (HGNC:2228): (catechol-O-methyltransferase) Catechol-O-methyltransferase catalyzes the transfer of a methyl group from S-adenosylmethionine to catecholamines, including the neurotransmitters dopamine, epinephrine, and norepinephrine. This O-methylation results in one of the major degradative pathways of the catecholamine transmitters. In addition to its role in the metabolism of endogenous substances, COMT is important in the metabolism of catechol drugs used in the treatment of hypertension, asthma, and Parkinson disease. COMT is found in two forms in tissues, a soluble form (S-COMT) and a membrane-bound form (MB-COMT). The differences between S-COMT and MB-COMT reside within the N-termini. Several transcript variants are formed through the use of alternative translation initiation sites and promoters. [provided by RefSeq, Sep 2008]

COMT links:

Genome browser will be placed here

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

GnomAd4 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	Protein	UniProt
COMT	NM_000754.4 linkuse as main transcript	c.186C>T	p.His62=	synonymous_variant	3/6	ENST00000361682.11	NP_000745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COMT	ENST00000361682.11 linkuse as main transcript	c.186C>T	p.His62=	synonymous_variant	3/6	1	NM_000754.4	ENSP00000354511	P2	P21964-1

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

67786

AN:

152012

Hom.:

15738

Cov.:

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

Cov.:

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

GnomAD4 genome

AF:

0.446

AC:

67797

AN:

152130

Hom.:

15737

Cov.:

AF XY:

0.445

AC XY:

33124

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.330

Gnomad4 AMR

AF:

0.405

Gnomad4 ASJ

AF:

0.460

Gnomad4 EAS

AF:

0.270

Gnomad4 SAS

AF:

0.456

Gnomad4 FIN

AF:

0.551

Gnomad4 NFE

AF:

0.518

Gnomad4 OTH

AF:

0.423

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:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 21486747) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.72

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over