Variant 22-19968739-GC-GCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000754.4(COMT):c.*10dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 1,594,670 control chromosomes in the GnomAD database, including 396,962 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31467 hom., cov: 0)

Exomes 𝑓: 0.71 ( 365495 hom. )

Consequence

COMT
NM_000754.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.06

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:

ARVCF (HGNC:):

ARVCF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 22-19968739-G-GC is Benign according to our data. Variant chr22-19968739-G-GC is described in ClinVar as [Benign]. Clinvar id is 256784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COMT	NM_000754.4 linkuse as main transcript	c.*10dup		3_prime_UTR_variant	6/6	ENST00000361682.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COMT	ENST00000361682.11 linkuse as main transcript	c.*10dup		3_prime_UTR_variant	6/6	1	NM_000754.4	P2	P21964-1

Frequencies

GnomAD3 genomes

AF:

0.630

AC:

95592

AN:

151788

Hom.:

31467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.612

Gnomad ASJ

AF:

0.693

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.656

Gnomad FIN

AF:

0.690

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.737

Gnomad OTH

AF:

0.662

GnomAD3 exomes

AF:

0.655

AC:

153113

AN:

233776

Hom.:

50917

AF XY:

0.664

AC XY:

85161

AN XY:

128224

show subpopulations

Gnomad AFR exome

AF:

0.433

Gnomad AMR exome

AF:

0.564

Gnomad ASJ exome

AF:

0.678

Gnomad EAS exome

AF:

0.528

Gnomad SAS exome

AF:

0.645

Gnomad FIN exome

AF:

0.677

Gnomad NFE exome

AF:

0.732

Gnomad OTH exome

AF:

0.687

GnomAD4 exome

AF:

0.709

AC:

1022605

AN:

1442766

Hom.:

365495

Cov.:

AF XY:

0.708

AC XY:

508283

AN XY:

717936

show subpopulations

Gnomad4 AFR exome

AF:

0.430

Gnomad4 AMR exome

AF:

0.568

Gnomad4 ASJ exome

AF:

0.680

Gnomad4 EAS exome

AF:

0.540

Gnomad4 SAS exome

AF:

0.646

Gnomad4 FIN exome

AF:

0.688

Gnomad4 NFE exome

AF:

0.736

Gnomad4 OTH exome

AF:

0.689

GnomAD4 genome

AF:

0.629

AC:

95601

AN:

151904

Hom.:

31467

Cov.:

AF XY:

0.627

AC XY:

46542

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.441

Gnomad4 AMR

AF:

0.611

Gnomad4 ASJ

AF:

0.693

Gnomad4 EAS

AF:

0.526

Gnomad4 SAS

AF:

0.656

Gnomad4 FIN

AF:

0.690

Gnomad4 NFE

AF:

0.737

Gnomad4 OTH

AF:

0.661

Alfa

AF:

0.635

Hom.:

3961

Bravo

AF:

0.610

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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