Variant 10-94775416-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000769.4(CYP2C19):c.358T>C(p.Trp120Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0024 in 1,614,036 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as drug response (★★★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 11 hom. )

Consequence

CYP2C19
NM_000769.4 missense

Scores

Clinical Significance

drug response practice guideline O:2

Conservation

PhyloP100: 5.24

Variant links:

Genes affected

CYP2C19 (HGNC:2621): (cytochrome P450 family 2 subfamily C member 19) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, omeprazole, diazepam and some barbiturates. Polymorphism within this gene is associated with variable ability to metabolize mephenytoin, known as the poor metabolizer and extensive metabolizer phenotypes. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. [provided by RefSeq, Jul 2008]

CYP2C19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 239 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C19	NM_000769.4 linkuse as main transcript	c.358T>C	p.Trp120Arg	missense_variant	3/9	ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CYP2C19	ENST00000371321.9 linkuse as main transcript	c.358T>C	p.Trp120Arg	missense_variant	3/9	1	NM_000769.4	ENSP00000360372	P1
CYP2C19	ENST00000480405.2 linkuse as main transcript	c.358T>C	p.Trp120Arg	missense_variant	3/3	1		ENSP00000483847
CYP2C19	ENST00000645461.1 linkuse as main transcript	n.1411T>C		non_coding_transcript_exon_variant	2/7

Frequencies

GnomAD3 genomes

AF:

0.00157

AC:

239

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00275

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00155

AC:

390

AN:

251484

Hom.:

AF XY:

0.00171

AC XY:

232

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000809

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00274

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00248

AC:

3628

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1744

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000580

Gnomad4 FIN exome

AF:

0.000581

Gnomad4 NFE exome

AF:

0.00303

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00157

AC:

239

AN:

152208

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.00275

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00249

Hom.:

Bravo

AF:

0.00146

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00154

AC:

187

EpiCase

AF:

0.00251

EpiControl

AF:

0.00213

ClinVar

Significance: drug response

Submissions summary: Other:2

Revision: practice guideline

LINK: link

Submissions by phenotype

not provided

Other:1

other, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Dec 28, 2015

- Variant classified as "other reportable" ??? variant is clinically benign (not associated with disease) but is reported when observed (e.g. pseudodeficiency alleles).

CYP2C19: no function

Other:1

drug response, practice guideline

curation

Clinical Pharmacogenetics Implementation Consortium

- Allele function

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.69

T;.

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Uncertain

0.28

MutationTaster

Benign

0.70

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-14

.;D

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.94

MutPred

0.84

Gain of disorder (P = 3e-04);Gain of disorder (P = 3e-04);

MVP

0.84

MPC

0.020

ClinPred

0.18

GERP RS

2.5

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over