rs9332381

Positions:

• chr22-19969030-C-G

Variant summary

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

The NM_000754.4(COMT):​c.*294C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0767 in 297,176 control chromosomes in the GnomAD database, including 1,679 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 0.10 (1391 hom., cov: 33)
  • Exomes 𝑓: 0.052 (288 hom.)
• Consequence: COMT NM_000754.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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]

ARVCF (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COMT	NM_000754.4	c.*294C>G		3_prime_UTR_variant	6/6	ENST00000361682.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COMT	ENST00000361682.11	c.*294C>G		3_prime_UTR_variant	6/6	1	NM_000754.4	P2

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15282 AN: 152132 Hom.: 1385 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0588

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.0679

Gnomad SAS AF: 0.0656

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0410

Gnomad OTH AF: 0.0844

GnomAD4 exome AF: 0.0516 AC: 7477 AN: 144926 Hom.: 288 Cov.: 0 AF XY: 0.0519 AC XY: 4065 AN XY: 78330

Gnomad4 AFR exome AF: 0.233

Gnomad4 AMR exome AF: 0.0490

Gnomad4 ASJ exome AF: 0.0314

Gnomad4 EAS exome AF: 0.0545

Gnomad4 SAS exome AF: 0.0640

Gnomad4 FIN exome AF: 0.0417

Gnomad4 NFE exome AF: 0.0409

Gnomad4 OTH exome AF: 0.0528

GnomAD4 genome AF: 0.101 AC: 15309 AN: 152250 Hom.: 1391 Cov.: 33 AF XY: 0.0992 AC XY: 7385 AN XY: 74430

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.0591

Gnomad4 ASJ AF: 0.0302

Gnomad4 EAS AF: 0.0680

Gnomad4 SAS AF: 0.0657

Gnomad4 FIN AF: 0.0524

Gnomad4 NFE AF: 0.0410

Gnomad4 OTH AF: 0.0835

Alfa AF: 0.0726 Hom.: 117

Bravo AF: 0.107

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs9332381; hg19: chr22-19956553;