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GeneBe

rs165599

Variant summary

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

The NM_000754.4(COMT):c.*522G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 154,512 control chromosomes in the GnomAD database, including 26,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

Frequency

Genomes: 𝑓 0.56 ( 25871 hom., cov: 33)
Exomes 𝑓: 0.59 ( 446 hom. )

Consequence

COMT
NM_000754.4 3_prime_UTR

Scores

2

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 0.0760
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COMTNM_000754.4 linkuse as main transcriptc.*522G>A 3_prime_UTR_variant 6/6 ENST00000361682.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COMTENST00000361682.11 linkuse as main transcriptc.*522G>A 3_prime_UTR_variant 6/61 NM_000754.4 P2P21964-1

Frequencies

GnomAD3 genomes
AF:
0.560
AC:
85081
AN:
151920
Hom.:
25878
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.316
Gnomad AMI
AF:
0.796
Gnomad AMR
AF:
0.541
Gnomad ASJ
AF:
0.609
Gnomad EAS
AF:
0.499
Gnomad SAS
AF:
0.568
Gnomad FIN
AF:
0.668
Gnomad MID
AF:
0.655
Gnomad NFE
AF:
0.694
Gnomad OTH
AF:
0.580
GnomAD4 exome
AF:
0.589
AC:
1456
AN:
2474
Hom.:
446
Cov.:
0
AF XY:
0.576
AC XY:
794
AN XY:
1378
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.452
Gnomad4 ASJ exome
AF:
0.556
Gnomad4 EAS exome
AF:
0.583
Gnomad4 SAS exome
AF:
0.474
Gnomad4 FIN exome
AF:
0.586
Gnomad4 NFE exome
AF:
0.640
Gnomad4 OTH exome
AF:
0.589
GnomAD4 genome
AF:
0.560
AC:
85076
AN:
152038
Hom.:
25871
Cov.:
33
AF XY:
0.558
AC XY:
41486
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.315
Gnomad4 AMR
AF:
0.540
Gnomad4 ASJ
AF:
0.609
Gnomad4 EAS
AF:
0.499
Gnomad4 SAS
AF:
0.567
Gnomad4 FIN
AF:
0.668
Gnomad4 NFE
AF:
0.694
Gnomad4 OTH
AF:
0.578
Alfa
AF:
0.665
Hom.:
51250
Bravo
AF:
0.538
Asia WGS
AF:
0.531
AC:
1846
AN:
3478

ClinVar

Significance: drug response
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Tramadol response Other:1
drug response, no assertion criteria providedresearchBruce Budowle Laboratory, University of North Texas Health Science CenterApr 28, 2018- T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
Cadd
Benign
1.8
Dann
Benign
0.47

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: rs165599; hg19: chr22-19956781; API