dbSNP rs9332129: CYP2C9:c.643-115A>G (chr10-94948993-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000771.4(CYP2C9):c.643-115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 531,770 control chromosomes in the GnomAD database, including 735 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 0.044 ( 456 hom., cov: 32)

Exomes 𝑓: 0.012 ( 279 hom. )

Consequence

CYP2C9
NM_000771.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.131

Publications

4 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.

BP4

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4 link	c.643-115A>G		intron_variant	Intron 4 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.643-115A>G	intron_variant	Intron 4 of 8	1	NM_000771.4	ENSP00000260682.6	P11712-1
CYP2C9	ENST00000473496.1 link	n.414-115A>G	intron_variant	Intron 3 of 3	2
CYP2C9	ENST00000643112.1 link	n.643-115A>G	intron_variant	Intron 4 of 7			ENSP00000496202.1	A0A2R8YF67

Frequencies

GnomAD3 genomes

AF:

0.0436

AC:

6620

AN:

151974

Hom.:

453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0571

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.0306

GnomAD4 exome

AF:

0.0121

AC:

4585

AN:

379676

Hom.:

279

AF XY:

0.0110

AC XY:

2189

AN XY:

199782

show subpopulations

African (AFR)

AF:

0.158

AC:

1454

AN:

9178

American (AMR)

AF:

0.00992

AC:

112

AN:

11294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11332

East Asian (EAS)

AF:

0.0990

AC:

2488

AN:

25130

South Asian (SAS)

AF:

0.00367

AC:

AN:

20696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32002

Middle Eastern (MID)

AF:

0.00549

AC:

AN:

1638

European-Non Finnish (NFE)

AF:

0.000469

AC:

116

AN:

247106

Other (OTH)

AF:

0.0155

AC:

330

AN:

21300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

190

379

569

758

948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.0436

AC:

6638

AN:

152094

Hom.:

456

Cov.:

AF XY:

0.0419

AC XY:

3117

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.144

AC:

5986

AN:

41476

American (AMR)

AF:

0.0147

AC:

224

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0570

AC:

295

AN:

5174

South Asian (SAS)

AF:

0.00518

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000515

AC:

AN:

67998

Other (OTH)

AF:

0.0345

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

296

591

887

1182

1478

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.0279

Hom.:

Bravo

AF:

0.0492

Asia WGS

AF:

0.0480

AC:

166

AN:

3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.1

(source)

DANN

Benign

0.64

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

Other links and lift over