rs165599

chr22-19969258-G-Achr22-19969258-G-C

Variant summary

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

The NM_000754(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 151920 control chromosomes in the gnomAD Genomes database, including 25878 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 ( 25878 hom., cov: 33)

Consequence

COMT
NM_000754 3_prime_UTR

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 0.0760

Links

COMT (HGNC:2228):

ARVCF (HGNC:):

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

GnomAd 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
COMT	NM_000754.4 linkuse as main transcript	c.*522G>A		3_prime_UTR_variant	6/6	ENST00000361682.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COMT	ENST00000361682.11 linkuse as main transcript	c.*522G>A		3_prime_UTR_variant	6/6	1	NM_000754.4	P2	P21964-1

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

85081

AN:

151920

Hom.:

25878

Cov.:

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

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

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 provided

research

Bruce Budowle Laboratory, University of North Texas Health Science Center

Apr 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

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over