Menu
GeneBe

rs737865

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000754.4(COMT):c.-92+701A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,086 control chromosomes in the GnomAD database, including 4,399 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 0.23 ( 4399 hom., cov: 32)

Consequence

COMT
NM_000754.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.200
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COMTNM_000754.4 linkuse as main transcriptc.-92+701A>G intron_variant ENST00000361682.11
COMTNM_001362828.2 linkuse as main transcriptc.-386+701A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COMTENST00000361682.11 linkuse as main transcriptc.-92+701A>G intron_variant 1 NM_000754.4 P2P21964-1

Frequencies

GnomAD3 genomes
AF:
0.233
AC:
35389
AN:
151968
Hom.:
4398
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.149
Gnomad AMI
AF:
0.166
Gnomad AMR
AF:
0.220
Gnomad ASJ
AF:
0.427
Gnomad EAS
AF:
0.274
Gnomad SAS
AF:
0.263
Gnomad FIN
AF:
0.187
Gnomad MID
AF:
0.329
Gnomad NFE
AF:
0.278
Gnomad OTH
AF:
0.256
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.233
AC:
35403
AN:
152086
Hom.:
4399
Cov.:
32
AF XY:
0.231
AC XY:
17154
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.149
Gnomad4 AMR
AF:
0.220
Gnomad4 ASJ
AF:
0.427
Gnomad4 EAS
AF:
0.273
Gnomad4 SAS
AF:
0.263
Gnomad4 FIN
AF:
0.187
Gnomad4 NFE
AF:
0.278
Gnomad4 OTH
AF:
0.257
Alfa
AF:
0.281
Hom.:
6729
Bravo
AF:
0.228
Asia WGS
AF:
0.271
AC:
944
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
Cadd
Benign
1.3
Dann
Benign
0.79
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs737865; hg19: chr22-19930121; API