Variant rs769224 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.597G>A(p.Pro199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 1,613,964 control chromosomes in the GnomAD database, including 799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 219 hom., cov: 33)

Exomes 𝑓: 0.025 ( 580 hom. )

Consequence

COMT
NM_000754.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.92

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=-0.84).

BP6

Variant 22-19964281-G-A is Benign according to our data. Variant chr22-19964281-G-A is described in ClinVar as [Benign]. Clinvar id is 828956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-19964281-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0909 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.597G>A	p.Pro199=	synonymous_variant	5/6	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.597G>A	p.Pro199=	synonymous_variant	5/6	1	NM_000754.4	ENSP00000354511	P2	P21964-1

Frequencies

GnomAD3 genomes

AF:

0.0432

AC:

6579

AN:

152172

Hom.:

219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0934

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0288

Gnomad ASJ

AF:

0.0208

Gnomad EAS

AF:

0.0644

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.0203

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0218

Gnomad OTH

AF:

0.0297

GnomAD3 exomes

AF:

0.0302

AC:

7592

AN:

251326

Hom.:

160

AF XY:

0.0282

AC XY:

3826

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0924

Gnomad AMR exome

AF:

0.0267

Gnomad ASJ exome

AF:

0.0205

Gnomad EAS exome

AF:

0.0696

Gnomad SAS exome

AF:

0.0210

Gnomad FIN exome

AF:

0.0198

Gnomad NFE exome

AF:

0.0217

Gnomad OTH exome

AF:

0.0231

GnomAD4 exome

AF:

0.0245

AC:

35875

AN:

1461674

Hom.:

580

Cov.:

AF XY:

0.0242

AC XY:

17580

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.0934

Gnomad4 AMR exome

AF:

0.0258

Gnomad4 ASJ exome

AF:

0.0215

Gnomad4 EAS exome

AF:

0.0533

Gnomad4 SAS exome

AF:

0.0219

Gnomad4 FIN exome

AF:

0.0172

Gnomad4 NFE exome

AF:

0.0219

Gnomad4 OTH exome

AF:

0.0276

GnomAD4 genome

AF:

0.0433

AC:

6589

AN:

152290

Hom.:

219

Cov.:

AF XY:

0.0431

AC XY:

3207

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0933

Gnomad4 AMR

AF:

0.0289

Gnomad4 ASJ

AF:

0.0208

Gnomad4 EAS

AF:

0.0645

Gnomad4 SAS

AF:

0.0205

Gnomad4 FIN

AF:

0.0203

Gnomad4 NFE

AF:

0.0218

Gnomad4 OTH

AF:

0.0294

Alfa

AF:

0.0258

Hom.:

150

Bravo

AF:

0.0462

Asia WGS

AF:

0.0380

AC:

134

AN:

3478

EpiCase

AF:

0.0215

EpiControl

AF:

0.0223

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 05, 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

-0.84

CADD

Benign

2.3

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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