rs7900194

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000771.4(CYP2C9):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 0.0033 in 1,613,840 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign,drug response (★★).

Frequency

Genomes: 𝑓 0.016 ( 81 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 74 hom. )

Consequence

CYP2C9
NM_000771.4 missense

Scores

Clinical Significance

Benign/Likely benign; drug response criteria provided, multiple submitters, no conflicts B:2O:3

Conservation

PhyloP100: -0.771

Publications

156 publications found

Variant links:

Genes affected

CYP2C9 (HGNC:2623): (cytochrome P450 family 2 subfamily C member 9) 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 its expression is induced by rifampin. The enzyme is known to metabolize many xenobiotics, including phenytoin, tolbutamide, ibuprofen and S-warfarin. Studies identifying individuals who are poor metabolizers of phenytoin and tolbutamide suggest that this gene is polymorphic. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. [provided by RefSeq, Jul 2008]

CYP2C9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048422813).

BP6

Variant 10-94942309-G-A is Benign according to our data. Variant chr10-94942309-G-A is described in ClinVar as Benign/Likely_benign|drug_response. ClinVar VariationId is 226024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4 link	c.449G>A	p.Arg150His	missense_variant	Exon 3 of 9	ENST00000260682.8	NP_000762.2	P11712-1S5RV20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8 link	c.449G>A	p.Arg150His	missense_variant	Exon 3 of 9	1	NM_000771.4	ENSP00000260682.6		P11712-1

Frequencies

GnomAD3 genomes

AF:

0.0158

AC:

2405

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0549

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.00862

GnomAD2 exomes

AF:

0.00440

AC:

1106

AN:

251202

AF XY:

0.00328

show subpopulations

Gnomad AFR exome

AF:

0.0589

Gnomad AMR exome

AF:

0.00203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000387

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00199

AC:

2913

AN:

1461596

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

1244

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.0594

AC:

1986

AN:

33462

American (AMR)

AF:

0.00217

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26124

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39686

South Asian (SAS)

AF:

0.000568

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000438

AC:

487

AN:

1111824

Other (OTH)

AF:

0.00446

AC:

269

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

199

398

597

796

995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.0159

AC:

2415

AN:

152244

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

1146

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0550

AC:

2284

AN:

41526

American (AMR)

AF:

0.00471

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5172

South Asian (SAS)

AF:

0.000829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000515

AC:

AN:

68016

Other (OTH)

AF:

0.00853

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

119

239

358

478

597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00460

Hom.:

Bravo

AF:

0.0179

ESP6500AA

AF:

0.0581

AC:

256

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.00524

AC:

636

EpiCase

AF:

0.000763

EpiControl

AF:

0.000533

ClinVar

Significance: Benign/Likely benign; drug response

Submissions summary: Benign:2Other:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 30, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25087612, 24118918, 22378156, 23376925, 23752738, 25142737, 25832633) -

Jul 03, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Piroxicam response

Other:1

Feb 11, 2019

Medical Genetics Summaries

Significance:drug response

Review Status:criteria provided, single submitter

Collection Method:curation

Individuals with 2 decreased function alleles (CYP2C9 poor metabolizers) have reduced clearance of piroxicam. Because the standard recommended dose of piroxicam may cause abnormally high plasma levels, a dose reduction should be considered for these individuals. Poor metabolizer

Lesinurad response

Other:1

Feb 11, 2019

Medical Genetics Summaries

Significance:drug response

Review Status:criteria provided, single submitter

Collection Method:curation

Lesinurad should be used with caution in individuals with 2 decreased function alleles (CYP2C9 poor metabolizers) because of increased exposure and an increased risk of side effects. Poor metabolizer

Flurbiprofen response

Other:1

Feb 11, 2019

Medical Genetics Summaries

Significance:drug response

Review Status:criteria provided, single submitter

Collection Method:curation

The dose of flurbiprofen should be reduced in individuals with 2 decreased function alleles (CYP2C9 poor metabolizers) to avoid abnormally high plasma levels due to reduced metabolic clearance. Poor metabolizer

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.7

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.097

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0082

LIST_S2

Benign

0.032

T;T

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L

PhyloP100

-0.77

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.5

.;N

REVEL

Benign

0.079

Sift

Benign

0.42

.;T

Sift4G

Benign

0.27

.;T

Polyphen

0.016

.;B

Vest4

0.12

MVP

0.58

MPC

0.0086

ClinPred

0.0040

GERP RS

-4.3

Varity_R

0.081

gMVP

0.080

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over