dbSNP rs2298037: CYP2C9:c.1291+147C>T (chr10-94986321-C-T) – 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.1291+147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 828,566 control chromosomes in the GnomAD database, including 14,225 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 0.14 ( 1923 hom., cov: 32)

Exomes 𝑓: 0.18 ( 12302 hom. )

Consequence

CYP2C9
NM_000771.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.876

Publications

11 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4 link	c.1291+147C>T		intron_variant	Intron 8 of 8	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.1291+147C>T		intron_variant	Intron 8 of 8	1	NM_000771.4	ENSP00000260682.6		P11712-1
CYP2C9	ENST00000643112.1 link	n.*300+147C>T		intron_variant	Intron 7 of 7			ENSP00000496202.1		A0A2R8YF67

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

21040

AN:

152042

Hom.:

1920

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0368

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.128

GnomAD4 exome

AF:

0.177

AC:

119852

AN:

676406

Hom.:

12302

AF XY:

0.184

AC XY:

65519

AN XY:

355910

show subpopulations

African (AFR)

AF:

0.0355

AC:

627

AN:

17652

American (AMR)

AF:

0.108

AC:

3396

AN:

31492

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

2534

AN:

18364

East Asian (EAS)

AF:

0.313

AC:

10343

AN:

33026

South Asian (SAS)

AF:

0.307

AC:

18224

AN:

59308

European-Finnish (FIN)

AF:

0.181

AC:

6509

AN:

36008

Middle Eastern (MID)

AF:

0.104

AC:

307

AN:

2950

European-Non Finnish (NFE)

AF:

0.163

AC:

72375

AN:

443598

Other (OTH)

AF:

0.163

AC:

5537

AN:

34008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5017

10034

15051

20068

25085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1388

2776

4164

5552

6940

<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:

0.138

AC:

21047

AN:

152160

Hom.:

1923

Cov.:

AF XY:

0.143

AC XY:

10653

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0367

AC:

1524

AN:

41548

American (AMR)

AF:

0.125

AC:

1917

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

485

AN:

3472

East Asian (EAS)

AF:

0.307

AC:

1588

AN:

5166

South Asian (SAS)

AF:

0.318

AC:

1533

AN:

4824

European-Finnish (FIN)

AF:

0.194

AC:

2048

AN:

10562

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.169

AC:

11463

AN:

67986

Other (OTH)

AF:

0.132

AC:

279

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

892

1785

2677

3570

4462

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<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:

0.152

Hom.:

3144

Bravo

AF:

0.125

Asia WGS

AF:

0.293

AC:

1017

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.090

(source)

DANN

Benign

0.43

PhyloP100

-0.88

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over