Genetic Variant CYP2C9:c.961+95A>G (chr10-94972340-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.961+95A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,432,778 control chromosomes in the GnomAD database, including 29,544 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 0.19 ( 3018 hom., cov: 32)

Exomes 𝑓: 0.20 ( 26526 hom. )

Consequence

CYP2C9
NM_000771.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.536

Publications

6 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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4 link	c.961+95A>G		intron_variant	Intron 6 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.961+95A>G		intron_variant	Intron 6 of 8	1	NM_000771.4	ENSP00000260682.6		P11712-1
CYP2C9	ENST00000643112.1 link	n.820-8843A>G		intron_variant	Intron 5 of 7			ENSP00000496202.1		A0A2R8YF67

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29258

AN:

152044

Hom.:

3017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.00945

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.193

GnomAD4 exome

AF:

0.197

AC:

252874

AN:

1280616

Hom.:

26526

AF XY:

0.198

AC XY:

127774

AN XY:

645310

show subpopulations

African (AFR)

AF:

0.198

AC:

5811

AN:

29340

American (AMR)

AF:

0.102

AC:

4290

AN:

42200

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

5196

AN:

24362

East Asian (EAS)

AF:

0.00880

AC:

339

AN:

38528

South Asian (SAS)

AF:

0.170

AC:

13713

AN:

80792

European-Finnish (FIN)

AF:

0.190

AC:

9576

AN:

50498

Middle Eastern (MID)

AF:

0.209

AC:

1120

AN:

5366

European-Non Finnish (NFE)

AF:

0.212

AC:

202498

AN:

955296

Other (OTH)

AF:

0.190

AC:

10331

AN:

54234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

9887

19773

29660

39546

49433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6466

12932

19398

25864

32330

<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:

0.192

AC:

29257

AN:

152162

Hom.:

3018

Cov.:

AF XY:

0.189

AC XY:

14077

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.200

AC:

8298

AN:

41534

American (AMR)

AF:

0.130

AC:

1988

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

738

AN:

3470

East Asian (EAS)

AF:

0.00947

AC:

AN:

5174

South Asian (SAS)

AF:

0.163

AC:

786

AN:

4818

European-Finnish (FIN)

AF:

0.182

AC:

1926

AN:

10590

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14761

AN:

67972

Other (OTH)

AF:

0.190

AC:

402

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1221

2442

3662

4883

6104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.203

Hom.:

9018

Bravo

AF:

0.188

Asia WGS

AF:

0.0840

AC:

291

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.8

(source)

DANN

Benign

0.72

PhyloP100

0.54

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