Genetic Variant ENST00000461906.1:c.*189G>A (chr10-94942538-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000461906.1(CYP2C9):c.*189G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 825,570 control chromosomes in the GnomAD database, including 19,597 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 0.24 ( 4413 hom., cov: 32)

Exomes 𝑓: 0.21 ( 15184 hom. )

Consequence

CYP2C9
ENST00000461906.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.90

Publications

12 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 (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4 link	c.481+197G>A		intron_variant	Intron 3 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.481+197G>A		intron_variant	Intron 3 of 8	1	NM_000771.4	ENSP00000260682.6		P11712-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35869

AN:

151998

Hom.:

4407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.0938

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.206

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.208

AC:

139999

AN:

673454

Hom.:

15184

Cov.:

AF XY:

0.207

AC XY:

72626

AN XY:

350486

show subpopulations

African (AFR)

AF:

0.284

AC:

4919

AN:

17344

American (AMR)

AF:

0.150

AC:

4602

AN:

30760

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

5203

AN:

18080

East Asian (EAS)

AF:

0.122

AC:

3967

AN:

32402

South Asian (SAS)

AF:

0.190

AC:

11279

AN:

59382

European-Finnish (FIN)

AF:

0.207

AC:

8664

AN:

41944

Middle Eastern (MID)

AF:

0.277

AC:

733

AN:

2650

European-Non Finnish (NFE)

AF:

0.213

AC:

93342

AN:

437364

Other (OTH)

AF:

0.217

AC:

7290

AN:

33528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

5454

10908

16363

21817

27271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1604

3208

4812

6416

8020

<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:

0.236

AC:

35899

AN:

152116

Hom.:

4413

Cov.:

AF XY:

0.232

AC XY:

17255

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.286

AC:

11861

AN:

41486

American (AMR)

AF:

0.200

AC:

3054

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

995

AN:

3470

East Asian (EAS)

AF:

0.0936

AC:

484

AN:

5170

South Asian (SAS)

AF:

0.195

AC:

939

AN:

4826

European-Finnish (FIN)

AF:

0.206

AC:

2178

AN:

10588

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.229

AC:

15580

AN:

67980

Other (OTH)

AF:

0.256

AC:

540

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1427

2854

4281

5708

7135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<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:

0.225

Hom.:

5681

Bravo

AF:

0.239

Asia WGS

AF:

0.167

AC:

580

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.97

(source)

DANN

Benign

0.55

PhyloP100

-1.9

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