rs740602

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

paroxysmal dyskinesia
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

COMT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
COMT	NM_000754.4 link	c.219G>A	p.Gln73Gln	synonymous_variant	Exon 3 of 6	ENST00000361682.11	NP_000745.1	P21964-1A0A140VJG8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMT	ENST00000361682.11 link	c.219G>A	p.Gln73Gln	synonymous_variant	Exon 3 of 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

GnomAD2 exomes

AF:

0.0198

AC:

4958

AN:

250570

AF XY:

0.0169

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 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

African (AFR)

AF:

0.184

AC:

6162

AN:

33478

American (AMR)

AF:

0.0146

AC:

654

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00253

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0184

AC:

1585

AN:

86252

European-Finnish (FIN)

AF:

0.00977

AC:

518

AN:

53014

Middle Eastern (MID)

AF:

0.0264

AC:

152

AN:

5766

European-Non Finnish (NFE)

AF:

0.00388

AC:

4311

AN:

1111748

Other (OTH)

AF:

0.0192

AC:

1160

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

813

1626

2440

3253

4066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

284

568

852

1136

1420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0561

AC:

8551

AN:

152312

Hom.:

676

Cov.:

AF XY:

0.0546

AC XY:

4067

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.179

AC:

7447

AN:

41540

American (AMR)

AF:

0.0272

AC:

417

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.0201

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00837

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00575

AC:

391

AN:

68032

Other (OTH)

AF:

0.0436

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

389

777

1166

1554

1943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0302

Hom.:

301

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

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Tramadol response

Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance:drug response

Review Status:no assertion criteria provided

Collection Method:research

- 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

(source)

DANN

Benign

0.83

PhyloP100

1.4

PromoterAI

-0.019

Neutral

(source)

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over