Variant chr10-94775367-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000769.4(CYP2C19):c.332-23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,612,890 control chromosomes in the GnomAD database, including 24,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.17 ( 2548 hom., cov: 32)

Exomes 𝑓: 0.16 ( 21944 hom. )

Consequence

CYP2C19
NM_000769.4 intron

Scores

Clinical Significance

drug response practice guideline O:1

Conservation

PhyloP100: 1.34

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 5 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C19	NM_000769.4 link	c.332-23A>G		intron_variant	Intron 2 of 8	ENST00000371321.9	NP_000760.1	P33261

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP2C19	ENST00000371321.9 link	c.332-23A>G	intron_variant	Intron 2 of 8	1	NM_000769.4	ENSP00000360372.3	P33261
CYP2C19	ENST00000480405.2 link	c.332-23A>G	intron_variant	Intron 2 of 2	1		ENSP00000483847.1	A0A087X125
ENSG00000276490	ENST00000464755.1 link	n.*90-23A>G	intron_variant	Intron 7 of 13	2		ENSP00000483243.1	A0A087X0B3
CYP2C19	ENST00000645461.1 link	n.1385-23A>G	intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26303

AN:

151746

Hom.:

2543

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.152

GnomAD3 exomes

AF:

0.180

AC:

45341

AN:

251244

Hom.:

4851

AF XY:

0.187

AC XY:

25439

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.199

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.134

Gnomad EAS exome

AF:

0.310

Gnomad SAS exome

AF:

0.327

Gnomad FIN exome

AF:

0.173

Gnomad NFE exome

AF:

0.147

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.164

AC:

239816

AN:

1461026

Hom.:

21944

Cov.:

AF XY:

0.169

AC XY:

122657

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.134

Gnomad4 EAS exome

AF:

0.303

Gnomad4 SAS exome

AF:

0.324

Gnomad4 FIN exome

AF:

0.173

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.173

AC:

26324

AN:

151864

Hom.:

2548

Cov.:

AF XY:

0.177

AC XY:

13157

AN XY:

74166

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.133

Gnomad4 EAS

AF:

0.312

Gnomad4 SAS

AF:

0.331

Gnomad4 FIN

AF:

0.185

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.146

Hom.:

445

Bravo

AF:

0.167

Asia WGS

AF:

0.305

AC:

1059

AN:

3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: practice guideline

LINK: link

Submissions by phenotype

CYP2C19: no function

Other:1

Clinical Pharmacogenetics Implementation Consortium

Significance: drug response

Review Status: practice guideline

Collection Method: curation

- Allele function

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.3

DANN

Benign

0.67

La Branchor

0.73

BranchPoint Hunter

5.0

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