rs5993883

Positions:

• chr22-19950115-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000754.4(COMT):​c.-92+8218T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,912 control chromosomes in the GnomAD database, including 18,706 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18706 hom., cov: 32)
• Consequence: COMT NM_000754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COMT	NM_000754.4	c.-92+8218T>G		intron_variant		ENST00000361682.11	NP_000745.1
COMT	NM_001362828.2	c.-386+8218T>G		intron_variant			NP_001349757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COMT	ENST00000361682.11	c.-92+8218T>G		intron_variant		1	NM_000754.4	ENSP00000354511.6

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74591 AN: 151794 Hom.: 18692 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.491 AC: 74644 AN: 151912 Hom.: 18706 Cov.: 32 AF XY: 0.485 AC XY: 36009 AN XY: 74270

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.537

Alfa AF: 0.524 Hom.: 43356

Bravo AF: 0.498

Asia WGS AF: 0.431 AC: 1500 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.36

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: rs5993883; hg19: chr22-19937638;