rs9306235

Positions:

• chr22-19967634-G-A
• chr22-19967634-G-T

Variant summary

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

The NM_000754.4(COMT):​c.616-902G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0511 in 310,602 control chromosomes in the GnomAD database, including 536 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 0.049 (238 hom., cov: 33)
  • Exomes 𝑓: 0.053 (298 hom.)
• Consequence: COMT NM_000754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COMT	NM_000754.4	c.616-902G>A		intron_variant		ENST00000361682.11	NP_000745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COMT	ENST00000361682.11	c.616-902G>A		intron_variant		1	NM_000754.4	ENSP00000354511	P2

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7421 AN: 152130 Hom.: 238 Cov.: 33

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0609

Gnomad ASJ AF: 0.0747

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.0483

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.0626

GnomAD4 exome AF: 0.0533 AC: 8448 AN: 158354 Hom.: 298 Cov.: 0 AF XY: 0.0489 AC XY: 4233 AN XY: 86482

Gnomad4 AFR exome AF: 0.0126

Gnomad4 AMR exome AF: 0.0462

Gnomad4 ASJ exome AF: 0.0675

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0144

Gnomad4 FIN exome AF: 0.0534

Gnomad4 NFE exome AF: 0.0725

Gnomad4 OTH exome AF: 0.0564

GnomAD4 genome AF: 0.0488 AC: 7424 AN: 152248 Hom.: 238 Cov.: 33 AF XY: 0.0474 AC XY: 3525 AN XY: 74430

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.0608

Gnomad4 ASJ AF: 0.0747

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.0483

Gnomad4 NFE AF: 0.0715

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0715 Hom.: 402

Bravo AF: 0.0497

Asia WGS AF: 0.00780 AC: 28 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9306235; hg19: chr22-19955157;