Variant chr10-94775507-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_StrongBS2

The NM_000769.4(CYP2C19):c.449G>A(p.Arg150His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,613,980 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. 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 0.0029 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 26 hom. )

Consequence

CYP2C19
NM_000769.4 missense

Scores

Clinical Significance

drug response practice guideline B:1O:1

Conservation

PhyloP100: -1.42

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005895734).

BP6

Variant 10-94775507-G-A is Benign according to our data. Variant chr10-94775507-G-A is described in ClinVar as [drug_response]. Clinvar id is 633845.Status of the report is practice_guideline, 4 stars. We mark this variant Likely_benign, oryginal submissions are: {drug_response=1, Likely_benign=1}.

BS2

High AC in GnomAd4 at 440 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C19	NM_000769.4 linkuse as main transcript	c.449G>A	p.Arg150His	missense_variant	3/9	ENST00000371321.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CYP2C19	ENST00000371321.9 linkuse as main transcript	c.449G>A	p.Arg150His	missense_variant	3/9	1	NM_000769.4	P1
CYP2C19	ENST00000480405.2 linkuse as main transcript	c.449G>A	p.Arg150His	missense_variant	3/3	1
CYP2C19	ENST00000645461.1 linkuse as main transcript	n.1502G>A		non_coding_transcript_exon_variant	2/7

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

439

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00528

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00269

AC:

676

AN:

251362

Hom.:

AF XY:

0.00277

AC XY:

376

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00507

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00520

AC:

7604

AN:

1461728

Hom.:

Cov.:

AF XY:

0.00501

AC XY:

3645

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00106

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.00643

Gnomad4 OTH exome

AF:

0.00422

GnomAD4 genome

AF:

0.00289

AC:

440

AN:

152252

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

193

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.00529

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00364

Hom.:

Bravo

AF:

0.00280

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00265

AC:

322

EpiCase

AF:

0.00545

EpiControl

AF:

0.00516

ClinVar

Significance: drug response

Submissions summary: Benign:1Other:1

Revision: practice guideline

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

CYP2C19: BP4, BS2 -

CYP2C19: normal 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

0.085

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.9

DANN

Benign

0.85

DEOGEN2

Benign

0.033

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.032

T;.

M_CAP

Benign

0.0058

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.4

.;N

REVEL

Benign

0.062

Sift

Benign

0.51

.;T

Sift4G

Benign

0.24

T;T

Vest4

0.034

MVP

0.26

MPC

0.0050

ClinPred

0.0020

GERP RS

-7.8

gMVP

0.17

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