rs6269

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.47
Variant links:
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]

Genome browser will be placed here

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
COMTNM_000754.4 linkuse as main transcriptc.1-98A>G intron_variant ENST00000361682.11 NP_000745.1
COMTNM_001362828.2 linkuse as main transcriptc.-98A>G 5_prime_UTR_variant 3/6 NP_001349757.1
COMTNM_001135161.2 linkuse as main transcriptc.1-98A>G intron_variant NP_001128633.1
COMTNM_001135162.2 linkuse as main transcriptc.1-98A>G intron_variant NP_001128634.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COMTENST00000361682.11 linkuse as main transcriptc.1-98A>G intron_variant 1 NM_000754.4 ENSP00000354511 P2P21964-1

Frequencies

GnomAD3 genomes
AF:
0.377
AC:
57285
AN:
152008
Hom.:
10884
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.375
Gnomad AMI
AF:
0.310
Gnomad AMR
AF:
0.331
Gnomad ASJ
AF:
0.475
Gnomad EAS
AF:
0.325
Gnomad SAS
AF:
0.330
Gnomad FIN
AF:
0.309
Gnomad MID
AF:
0.424
Gnomad NFE
AF:
0.401
Gnomad OTH
AF:
0.396
GnomAD4 exome
AF:
0.392
AC:
536868
AN:
1369392
Hom.:
106561
Cov.:
30
AF XY:
0.392
AC XY:
263406
AN XY:
672754
show subpopulations
Gnomad4 AFR exome
AF:
0.368
Gnomad4 AMR exome
AF:
0.244
Gnomad4 ASJ exome
AF:
0.462
Gnomad4 EAS exome
AF:
0.295
Gnomad4 SAS exome
AF:
0.339
Gnomad4 FIN exome
AF:
0.325
Gnomad4 NFE exome
AF:
0.405
Gnomad4 OTH exome
AF:
0.397
GnomAD4 genome
AF:
0.377
AC:
57316
AN:
152126
Hom.:
10887
Cov.:
33
AF XY:
0.372
AC XY:
27645
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.375
Gnomad4 AMR
AF:
0.331
Gnomad4 ASJ
AF:
0.475
Gnomad4 EAS
AF:
0.324
Gnomad4 SAS
AF:
0.330
Gnomad4 FIN
AF:
0.309
Gnomad4 NFE
AF:
0.401
Gnomad4 OTH
AF:
0.396
Alfa
AF:
0.376
Hom.:
3423
Bravo
AF:
0.378
Asia WGS
AF:
0.327
AC:
1141
AN:
3478

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 submitterclinical testingGeneDxMay 10, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.68
DANN
Benign
0.39

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6269; hg19: chr22-19949952; COSMIC: COSV52891062; COSMIC: COSV52891062; API