Genetic Variant CYP2C19:p.Trp120Arg (chr10-94775416-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -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 (★★★★).

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

Publications

121 publications found

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:

ENSG00000276490 (HGNC:):

ENSG00000276490 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 239 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000769.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C19	NM_000769.4	MANE Select	c.358T>C	p.Trp120Arg	missense	Exon 3 of 9	NP_000760.1	P33261

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP2C19	ENST00000371321.9	TSL:1 MANE Select	c.358T>C	p.Trp120Arg	missense	Exon 3 of 9	ENSP00000360372.3	P33261
CYP2C19	ENST00000480405.2	TSL:1	c.358T>C	p.Trp120Arg	missense	Exon 3 of 3	ENSP00000483847.1	A0A087X125
ENSG00000276490	ENST00000464755.1	TSL:2	n.*116T>C		non_coding_transcript_exon	Exon 8 of 14	ENSP00000483243.1	A0A087X0B3

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

GnomAD2 exomes

AF:

0.00155

AC:

390

AN:

251484

AF XY:

0.00171

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 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

African (AFR)

AF:

0.000299

AC:

AN:

33480

American (AMR)

AF:

0.000738

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000580

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.000581

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00303

AC:

3365

AN:

1112004

Other (OTH)

AF:

0.00215

AC:

130

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

251

503

754

1006

1257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00157

AC:

239

AN:

152208

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

41538

American (AMR)

AF:

0.00131

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000831

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.000378

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00275

AC:

187

AN:

68014

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00226

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

ClinVar submissions as Germline

Significance:drug response

Revision:practice guideline

View on ClinVar

Pathogenic

VUS

Benign

Condition

CYP2C19: no function (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.69

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.51

MetaSVM

Uncertain

0.28

PhyloP100

5.2

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-14

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.94

MutPred

0.84

Gain of disorder (P = 3e-04)

MVP

0.84

MPC

0.020

ClinPred

0.18

GERP RS

2.5

gMVP

0.65

Mutation Taster

=19/81

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over