Genetic Variant CYP2C9:c.482-28G>A (chr10-94947751-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000771.4(CYP2C9):c.482-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00048 in 1,609,144 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 2 hom. )

Consequence

CYP2C9
NM_000771.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.810

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BS2

High AC in GnomAd4 at 300 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4 link	c.482-28G>A		intron_variant	Intron 3 of 8	ENST00000260682.8	NP_000762.2	P11712-1S5RV20

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP2C9	ENST00000260682.8 link	c.482-28G>A	intron_variant	Intron 3 of 8	1	NM_000771.4	ENSP00000260682.6	P11712-1
CYP2C9	ENST00000473496.1 link	n.253-28G>A	intron_variant	Intron 2 of 3	2
CYP2C9	ENST00000643112.1 link	n.482-28G>A	intron_variant	Intron 3 of 7			ENSP00000496202.1	A0A2R8YF67
CYP2C9	ENST00000645207.1 link	n.635-28G>A	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00191

AC:

291

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00609

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.000755

AC:

189

AN:

250204

AF XY:

0.000621

show subpopulations

Gnomad AFR exome

AF:

0.00660

Gnomad AMR exome

AF:

0.000465

Gnomad ASJ exome

AF:

0.00417

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.000325

AC:

473

AN:

1456954

Hom.:

Cov.:

AF XY:

0.000298

AC XY:

216

AN XY:

724936

show subpopulations

African (AFR)

AF:

0.00645

AC:

215

AN:

33314

American (AMR)

AF:

0.000403

AC:

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00430

AC:

112

AN:

26072

East Asian (EAS)

AF:

0.00

AC:

AN:

39578

South Asian (SAS)

AF:

0.0000349

AC:

AN:

86024

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00259

AC:

AN:

4240

European-Non Finnish (NFE)

AF:

0.0000550

AC:

AN:

1109646

Other (OTH)

AF:

0.000865

AC:

AN:

60092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

101

126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00197

AC:

300

AN:

152190

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

133

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.00628

AC:

261

AN:

41532

American (AMR)

AF:

0.000590

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00404

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68014

Other (OTH)

AF:

0.00332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00224

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.5

(source)

DANN

Benign

0.29

PhyloP100

-0.81

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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10-94947751-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over