Variant 10-94775106-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000769.4(CYP2C19):c.217C>T(p.Arg73Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,614,092 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★★).

Frequency

Genomes: 𝑓 0.00088 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 2 hom. )

Consequence

CYP2C19
NM_000769.4 missense

Scores

Clinical Significance

drug response practice guideline O:1

Conservation

PhyloP100: 1.49

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0194951).

BS2

High AC in GnomAd4 at 134 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C19	NM_000769.4 linkuse as main transcript	c.217C>T	p.Arg73Cys	missense_variant	2/9	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.217C>T	p.Arg73Cys	missense_variant	2/9	1	NM_000769.4	ENSP00000360372	P1
CYP2C19	ENST00000480405.2 linkuse as main transcript	c.217C>T	p.Arg73Cys	missense_variant	2/3	1		ENSP00000483847
CYP2C19	ENST00000645461.1 linkuse as main transcript	n.1270C>T		non_coding_transcript_exon_variant	1/7

Frequencies

GnomAD3 genomes

AF:

0.000881

AC:

134

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000266

AC:

AN:

251462

Hom.:

AF XY:

0.000213

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000140

AC:

204

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00227

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000773

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000880

AC:

134

AN:

152230

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00284

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000249

Hom.:

Bravo

AF:

0.000888

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000255

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: practice guideline

LINK: link

Submissions by phenotype

CYP2C19: uncertain 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

Benign

0.22

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.82

T;.

M_CAP

Benign

0.0091

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.55

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.7

.;N

REVEL

Benign

0.13

Sift

Uncertain

0.0050

.;D

Sift4G

Uncertain

0.0020

D;D

Vest4

0.26

MVP

0.44

MPC

0.016

ClinPred

0.040

GERP RS

3.7

gMVP

0.42

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.

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