rs6269
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
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
NM_000754.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.47
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COMT | NM_000754.4 | c.1-98A>G | intron_variant | ENST00000361682.11 | NP_000745.1 | |||
COMT | NM_001362828.2 | c.-98A>G | 5_prime_UTR_variant | 3/6 | NP_001349757.1 | |||
COMT | NM_001135161.2 | c.1-98A>G | intron_variant | NP_001128633.1 | ||||
COMT | NM_001135162.2 | c.1-98A>G | intron_variant | NP_001128634.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COMT | ENST00000361682.11 | c.1-98A>G | intron_variant | 1 | NM_000754.4 | ENSP00000354511 | P2 |
Frequencies
GnomAD3 genomes AF: 0.377 AC: 57285AN: 152008Hom.: 10884 Cov.: 33
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GnomAD4 exome AF: 0.392 AC: 536868AN: 1369392Hom.: 106561 Cov.: 30 AF XY: 0.392 AC XY: 263406AN XY: 672754
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GnomAD4 genome AF: 0.377 AC: 57316AN: 152126Hom.: 10887 Cov.: 33 AF XY: 0.372 AC XY: 27645AN XY: 74372
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 10, 2021 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at