rs4244285

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000769.4(CYP2C19):c.681G>A(p.Pro227Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,464,646 control chromosomes in the GnomAD database, including 20,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign,other (★★). Synonymous variant affecting the same amino acid position (i.e. P227P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.17 ( 2363 hom., cov: 32)

Exomes 𝑓: 0.16 ( 18379 hom. )

Consequence

CYP2C19
NM_000769.4 synonymous

Scores

Clinical Significance

Likely benign; other criteria provided, multiple submitters, no conflicts B:2O:5

Conservation

PhyloP100: -0.801

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: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C19	NM_000769.4 link	c.681G>A	p.Pro227Pro	synonymous_variant	Exon 5 of 9	ENST00000371321.9	NP_000760.1	P33261

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP2C19	ENST00000371321.9 link	c.681G>A	p.Pro227Pro	synonymous_variant	Exon 5 of 9	1	NM_000769.4	ENSP00000360372.3	P33261
ENSG00000276490	ENST00000464755.1 link	n.*439G>A		non_coding_transcript_exon_variant	Exon 10 of 14	2		ENSP00000483243.1	A0A087X0B3
ENSG00000276490	ENST00000464755.1 link	n.*439G>A		3_prime_UTR_variant	Exon 10 of 14	2		ENSP00000483243.1	A0A087X0B3
CYP2C19	ENST00000645461.1 link	n.1734G>A		non_coding_transcript_exon_variant	Exon 4 of 7

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25424

AN:

151376

Hom.:

2358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.0865

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.149

GnomAD2 exomes

AF:

0.176

AC:

28518

AN:

161670

AF XY:

0.181

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.0991

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.307

Gnomad FIN exome

AF:

0.174

Gnomad NFE exome

AF:

0.147

Gnomad OTH exome

AF:

0.153

GnomAD4 exome

AF:

0.159

AC:

209244

AN:

1313152

Hom.:

18379

Cov.:

AF XY:

0.163

AC XY:

105482

AN XY:

648108

show subpopulations

Gnomad4 AFR exome

AF:

0.180

AC:

4669

AN:

25872

Gnomad4 AMR exome

AF:

0.104

AC:

2042

AN:

19654

Gnomad4 ASJ exome

AF:

0.132

AC:

2866

AN:

21636

Gnomad4 EAS exome

AF:

0.302

AC:

9559

AN:

31626

Gnomad4 SAS exome

AF:

0.319

AC:

19359

AN:

60616

Gnomad4 FIN exome

AF:

0.173

AC:

8799

AN:

50984

Gnomad4 NFE exome

AF:

0.146

AC:

152480

AN:

1043430

Gnomad4 Remaining exome

AF:

0.164

AC:

8884

AN:

54018

Heterozygous variant carriers

7332

14663

21995

29326

36658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

5806

11612

17418

23224

29030

<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:

0.168

AC:

25442

AN:

151494

Hom.:

2363

Cov.:

AF XY:

0.172

AC XY:

12754

AN XY:

73968

show subpopulations

Gnomad4 AFR

AF:

0.177

AC:

0.177123

AN:

0.177123

Gnomad4 AMR

AF:

0.130

AC:

0.130106

AN:

0.130106

Gnomad4 ASJ

AF:

0.132

AC:

0.132005

AN:

0.132005

Gnomad4 EAS

AF:

0.312

AC:

0.31187

AN:

0.31187

Gnomad4 SAS

AF:

0.332

AC:

0.332218

AN:

0.332218

Gnomad4 FIN

AF:

0.186

AC:

0.1865

AN:

0.1865

Gnomad4 NFE

AF:

0.148

AC:

0.147951

AN:

0.147951

Gnomad4 OTH

AF:

0.153

AC:

0.153226

AN:

0.153226

Heterozygous variant carriers

1066

2133

3199

4266

5332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.151

Hom.:

4719

Bravo

AF:

0.160

Asia WGS

AF:

0.302

AC:

1046

AN:

3474

ClinVar

Significance: Likely benign; other

Submissions summary: Benign:2Other:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 07, 2018

Eurofins Ntd Llc (ga)

Significance:other

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Clopidogrel response

Other:2

Faculty of Pharmacy, Damascus University

Significance:drug response

Review Status:no assertion criteria provided

Collection Method:research

rs4244285 is a SNP in the CYP2C19 gene and is linked to poor clopidogrel metabolic activation. rs4244285 is associated with reduced enzyme activity of CYP2C19 and lower concentration of clopidogrel active metabolite. likely responsive

May 14, 2018

OMIM

Significance:drug response

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not specified

Benign:1

Mar 09, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Proguanil, poor metabolism of

Other:1

Jun 01, 2009

OMIM

Significance:drug response

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Mephenytoin, poor metabolism of

Other:1

Jun 01, 2009

OMIM

Significance:drug response

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.39

Mutation Taster

=100/0

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.99

Position offset: 2

DS_AL_spliceai

0.89

Position offset: -38

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