dbSNP rs5844402: COMT:c.-92+2011delG (chr22-19943901-AG-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000754.4(COMT):c.-92+2011delG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 25065 hom., cov: 0)

Consequence

COMT
NM_000754.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

2 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

new If you want to explore the variant's impact on the transcript NM_000754.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000754.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMT	NM_000754.4	MANE Select	c.-92+2011delG		intron	N/A	NP_000745.1	P21964-1
	COMT	NM_001362828.2		c.-386+2011delG		intron	N/A	NP_001349757.1	P21964-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COMT	ENST00000361682.11	TSL:1 MANE Select	c.-92+2005delG	intron	N/A	ENSP00000354511.6	P21964-1
COMT	ENST00000964897.1		c.-92+2005delG	intron	N/A	ENSP00000634956.1
COMT	ENST00000678769.1		c.-92+2005delG	intron	N/A	ENSP00000503289.1	A0A7I2V370

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86816

AN:

151666

Hom.:

25035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.549

Gnomad AMI

AF:

0.491

Gnomad AMR

AF:

0.649

Gnomad ASJ

AF:

0.713

Gnomad EAS

AF:

0.710

Gnomad SAS

AF:

0.636

Gnomad FIN

AF:

0.478

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.562

Gnomad OTH

AF:

0.617

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.573

AC:

86899

AN:

151788

Hom.:

25065

Cov.:

AF XY:

0.574

AC XY:

42603

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.549

AC:

22706

AN:

41352

American (AMR)

AF:

0.649

AC:

9899

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.713

AC:

2470

AN:

3466

East Asian (EAS)

AF:

0.709

AC:

3643

AN:

5140

South Asian (SAS)

AF:

0.636

AC:

3055

AN:

4802

European-Finnish (FIN)

AF:

0.478

AC:

5042

AN:

10538

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.562

AC:

38166

AN:

67916

Other (OTH)

AF:

0.618

AC:

1307

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1890

3780

5669

7559

9449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<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:

0.360

Hom.:

631

Bravo

AF:

0.588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=100/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over