22-19943901-AG-A

Position:

• chr22-19943901-AG-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000754.4(COMT):​c.-92+2011del 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COMT	NM_000754.4	c.-92+2011del		intron_variant		ENST00000361682.11
COMT	NM_001362828.2	c.-386+2011del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COMT	ENST00000361682.11	c.-92+2011del		intron_variant		1	NM_000754.4	P2

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86816 AN: 151666 Hom.: 25035 Cov.: 0

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.: 0 AF XY: 0.574 AC XY: 42603 AN XY: 74166

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.562

Gnomad4 OTH AF: 0.618

Alfa AF: 0.360 Hom.: 631

Bravo AF: 0.588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs5844402; hg19: chr22-19931424;