NM_000771.4:c.1080C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000771.4(CYP2C9):c.1080C>G(p.Asp360Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00059 in 1,613,930 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign,drug response,other (★★).

Frequency

Genomes: 𝑓 0.0032 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

CYP2C9
NM_000771.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.47

Publications

161 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0100749135).

BP6

Variant 10-94981301-C-G is Benign according to our data. Variant chr10-94981301-C-G is described in ClinVar as Benign/Likely_benign|drug_response|other. ClinVar VariationId is 225984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 490 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000771.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C9	NM_000771.4	MANE Select	c.1080C>G	p.Asp360Glu	missense	Exon 7 of 9	NP_000762.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP2C9	ENST00000260682.8	TSL:1 MANE Select	c.1080C>G	p.Asp360Glu	missense	Exon 7 of 9	ENSP00000260682.6	P11712-1
CYP2C9	ENST00000880948.1		c.1101C>G	p.Asp367Glu	missense	Exon 7 of 9	ENSP00000551007.1
CYP2C9	ENST00000880956.1		c.1101C>G	p.Asp367Glu	missense	Exon 7 of 9	ENSP00000551015.1

Frequencies

GnomAD3 genomes

AF:

0.00323

AC:

491

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.000820

AC:

206

AN:

251170

AF XY:

0.000641

show subpopulations

Gnomad AFR exome

AF:

0.0109

Gnomad AMR exome

AF:

0.000609

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000317

AC:

463

AN:

1461664

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

202

AN XY:

727140

show subpopulations

African (AFR)

AF:

0.0101

AC:

338

AN:

33466

American (AMR)

AF:

0.000627

AC:

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000252

AC:

AN:

1111892

Other (OTH)

AF:

0.000911

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

130

163

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:

0.00322

AC:

490

AN:

152266

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

241

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0112

AC:

464

AN:

41558

American (AMR)

AF:

0.00105

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

108

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:

0.000195

Hom.:

Bravo

AF:

0.00361

ESP6500AA

AF:

0.0107

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00116

AC:

141

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign/Likely benign; drug response; other

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Flurbiprofen response (1)

Lesinurad response (1)

Piroxicam response (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.78

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

4.2

PhyloP100

-1.5

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.082

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

0.96

Vest4

0.30

MutPred

0.26

Gain of glycosylation at P363 (P = 0.0839)

MVP

0.52

MPC

0.049

ClinPred

0.14

GERP RS

-0.53

Varity_R

0.95

gMVP

0.063

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over