Variant rs6269 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000754.4(COMT):c.1-98A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,521,518 control chromosomes in the GnomAD database, including 117,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 10887 hom., cov: 33)

Exomes 𝑓: 0.39 ( 106561 hom. )

Consequence

COMT
NM_000754.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.47

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 22-19962429-A-G is Benign according to our data. Variant chr22-19962429-A-G is described in ClinVar as [Benign]. Clinvar id is 1275060.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
COMT	NM_000754.4 linkuse as main transcript	c.1-98A>G	intron_variant		ENST00000361682.11
COMT	NM_001362828.2 linkuse as main transcript	c.-98A>G	5_prime_UTR_variant	3/6
COMT	NM_001135161.2 linkuse as main transcript	c.1-98A>G	intron_variant
COMT	NM_001135162.2 linkuse as main transcript	c.1-98A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COMT	ENST00000361682.11 linkuse as main transcript	c.1-98A>G		intron_variant		1	NM_000754.4	P2	P21964-1

Frequencies

GnomAD3 genomes

AF:

0.377

AC:

57285

AN:

152008

Hom.:

10884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.475

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.401

Gnomad OTH

AF:

0.396

GnomAD4 exome

AF:

0.392

AC:

536868

AN:

1369392

Hom.:

106561

Cov.:

AF XY:

0.392

AC XY:

263406

AN XY:

672754

show subpopulations

Gnomad4 AFR exome

AF:

0.368

Gnomad4 AMR exome

AF:

0.244

Gnomad4 ASJ exome

AF:

0.462

Gnomad4 EAS exome

AF:

0.295

Gnomad4 SAS exome

AF:

0.339

Gnomad4 FIN exome

AF:

0.325

Gnomad4 NFE exome

AF:

0.405

Gnomad4 OTH exome

AF:

0.397

GnomAD4 genome

AF:

0.377

AC:

57316

AN:

152126

Hom.:

10887

Cov.:

AF XY:

0.372

AC XY:

27645

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.375

Gnomad4 AMR

AF:

0.331

Gnomad4 ASJ

AF:

0.475

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.330

Gnomad4 FIN

AF:

0.309

Gnomad4 NFE

AF:

0.401

Gnomad4 OTH

AF:

0.396

Alfa

AF:

0.376

Hom.:

3423

Bravo

AF:

0.378

Asia WGS

AF:

0.327

AC:

1141

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.68

DANN

Benign

0.39

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