Genetic Variant CYP2C9:c.168+83T>C (chr10-94938933-T-C) – 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.168+83T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,439,892 control chromosomes in the GnomAD database, including 29,433 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 ( 2965 hom., cov: 32)

Exomes 𝑓: 0.20 ( 26468 hom. )

Consequence

CYP2C9
NM_000771.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.48

Publications

10 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=-1.0).

BA1

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

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.168+83T>C		intron	N/A	NP_000762.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYP2C9	ENST00000260682.8	TSL:1 MANE Select	c.168+83T>C	intron	N/A	ENSP00000260682.6	P11712-1
CYP2C9	ENST00000461906.1	TSL:1	c.168+83T>C	intron	N/A	ENSP00000495649.1	P11712-2
CYP2C9	ENST00000880948.1		c.168+83T>C	intron	N/A	ENSP00000551007.1

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29024

AN:

152078

Hom.:

2964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.00942

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.191

GnomAD4 exome

AF:

0.197

AC:

253661

AN:

1287696

Hom.:

26468

AF XY:

0.198

AC XY:

128470

AN XY:

649954

show subpopulations

African (AFR)

AF:

0.193

AC:

5760

AN:

29886

American (AMR)

AF:

0.102

AC:

4511

AN:

44230

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

5372

AN:

25014

East Asian (EAS)

AF:

0.00889

AC:

344

AN:

38678

South Asian (SAS)

AF:

0.170

AC:

13971

AN:

82306

European-Finnish (FIN)

AF:

0.189

AC:

9967

AN:

52670

Middle Eastern (MID)

AF:

0.207

AC:

1025

AN:

4946

European-Non Finnish (NFE)

AF:

0.212

AC:

202338

AN:

955490

Other (OTH)

AF:

0.190

AC:

10373

AN:

54476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

10222

20444

30666

40888

51110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6400

12800

19200

25600

32000

<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:

0.191

AC:

29021

AN:

152196

Hom.:

2965

Cov.:

AF XY:

0.188

AC XY:

13974

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.195

AC:

8082

AN:

41526

American (AMR)

AF:

0.129

AC:

1972

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

735

AN:

3468

East Asian (EAS)

AF:

0.00944

AC:

AN:

5190

South Asian (SAS)

AF:

0.163

AC:

786

AN:

4818

European-Finnish (FIN)

AF:

0.182

AC:

1927

AN:

10596

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14762

AN:

67996

Other (OTH)

AF:

0.189

AC:

399

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1253

2505

3758

5010

6263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.202

Hom.:

9081

Bravo

AF:

0.186

Asia WGS

AF:

0.0830

AC:

290

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.41

(source)

DANN

Benign

0.52

PhyloP100

-2.5

PromoterAI

-0.0071

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over