rs9332131

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_000771.4(CYP2C9):c.818delA(p.Lys273ArgfsTer34) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000648 in 1,608,842 control chromosomes in the GnomAD database, including 5 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign,drug response,other (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 2 hom. )

Consequence

CYP2C9
NM_000771.4 frameshift, splice_region

Scores

Not classified

Clinical Significance

Benign/Likely benign; drug response; other criteria provided, multiple submitters, no conflicts B:2O:4

Conservation

PhyloP100: -1.21

Publications

100 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 -12 ACMG points.

BP6

Variant 10-94949281-GA-G is Benign according to our data. Variant chr10-94949281-GA-G is described in ClinVar as Benign/Likely_benign|drug_response|other. ClinVar VariationId is 285601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 472 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4 link	c.818delA	p.Lys273ArgfsTer34	frameshift_variant, splice_region_variant	Exon 5 of 9	ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CYP2C9	ENST00000260682.8 link	c.818delA	p.Lys273ArgfsTer34	frameshift_variant, splice_region_variant	Exon 5 of 9	1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000473496.1 link	n.589delA		non_coding_transcript_exon_variant	Exon 4 of 4	2
CYP2C9	ENST00000643112.1 link	n.818delA		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 8			ENSP00000496202.1

Frequencies

GnomAD3 genomes

AF:

0.00310

AC:

472

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

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:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000757

AC:

189

AN:

249618

AF XY:

0.000541

show subpopulations

Gnomad AFR exome

AF:

0.0106

Gnomad AMR exome

AF:

0.000264

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000392

AC:

571

AN:

1456612

Hom.:

Cov.:

AF XY:

0.000342

AC XY:

248

AN XY:

724694

show subpopulations

African (AFR)

AF:

0.0126

AC:

420

AN:

33280

American (AMR)

AF:

0.000496

AC:

AN:

44392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26006

East Asian (EAS)

AF:

0.00

AC:

AN:

39382

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53314

Middle Eastern (MID)

AF:

0.000371

AC:

AN:

5396

European-Non Finnish (NFE)

AF:

0.0000793

AC:

AN:

1109076

Other (OTH)

AF:

0.000632

AC:

AN:

60140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

110

137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00310

AC:

472

AN:

152230

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

232

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0108

AC:

449

AN:

41564

American (AMR)

AF:

0.00105

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68016

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000384

Hom.:

Bravo

AF:

0.00375

Asia WGS

AF:

0.000578

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign; drug response; other

Submissions summary: Benign:2Other:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Dec 28, 2015

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).

Aug 06, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 14, 2021

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

PhyloP100

-1.2

Mutation Taster

=29/171

disease causing (fs/PTC)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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