Variant rs740602 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000754.4(COMT):c.219G>A(p.Gln73Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,613,482 control chromosomes in the GnomAD database, including 1,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 676 hom., cov: 33)

Exomes 𝑓: 0.010 ( 626 hom. )

Consequence

COMT
NM_000754.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 1.35

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:

COMT (HGNC:):

COMT 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=-0.51).

BP6

Variant 22-19962745-G-A is Benign according to our data. Variant chr22-19962745-G-A is described in ClinVar as [Benign]. Clinvar id is 828971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 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.219G>A	p.Gln73Gln	synonymous_variant	3/6	ENST00000361682.11	NP_000745.1	P21964-1A0A140VJG8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COMT	ENST00000361682.11 linkuse as main transcript	c.219G>A	p.Gln73Gln	synonymous_variant	3/6	1	NM_000754.4	ENSP00000354511.6		P21964-1

Frequencies

GnomAD3 genomes

AF:

0.0560

AC:

8521

AN:

152194

Hom.:

671

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0273

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.00837

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00575

Gnomad OTH

AF:

0.0440

GnomAD3 exomes

AF:

0.0198

AC:

4958

AN:

250570

Hom.:

303

AF XY:

0.0169

AC XY:

2297

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.184

Gnomad AMR exome

AF:

0.0130

Gnomad ASJ exome

AF:

0.00359

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0179

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.00549

Gnomad OTH exome

AF:

0.0162

GnomAD4 exome

AF:

0.0100

AC:

14608

AN:

1461170

Hom.:

626

Cov.:

AF XY:

0.00972

AC XY:

7065

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.184

Gnomad4 AMR exome

AF:

0.0146

Gnomad4 ASJ exome

AF:

0.00253

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0184

Gnomad4 FIN exome

AF:

0.00977

Gnomad4 NFE exome

AF:

0.00388

Gnomad4 OTH exome

AF:

0.0192

GnomAD4 genome

AF:

0.0561

AC:

8551

AN:

152312

Hom.:

676

Cov.:

AF XY:

0.0546

AC XY:

4067

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.179

Gnomad4 AMR

AF:

0.0272

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0201

Gnomad4 FIN

AF:

0.00837

Gnomad4 NFE

AF:

0.00575

Gnomad4 OTH

AF:

0.0436

Alfa

AF:

0.0335

Hom.:

188

Bravo

AF:

0.0639

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.00594

EpiControl

AF:

0.00735

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
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

-0.51

CADD

Benign

6.3

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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