dbSNP rs1934969: CYP2C9:c.1292-109A>T (chr10-94988738-A-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.1292-109A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,155,416 control chromosomes in the GnomAD database, including 191,731 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 0.58 ( 26644 hom., cov: 32)

Exomes 𝑓: 0.57 ( 165087 hom. )

Consequence

CYP2C9
NM_000771.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.285

Publications

15 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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4 link	c.1292-109A>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.1292-109A>T		intron_variant	Intron 8 of 8	1	NM_000771.4	ENSP00000260682.6		P11712-1
CYP2C9	ENST00000643112.1 link	n.*301-109A>T		intron_variant	Intron 7 of 7			ENSP00000496202.1		A0A2R8YF67

Frequencies

GnomAD3 genomes

AF:

0.585

AC:

88811

AN:

151808

Hom.:

26627

Cov.:

show subpopulations

Gnomad AFR

AF:

0.668

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.576

Gnomad EAS

AF:

0.408

Gnomad SAS

AF:

0.640

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.561

Gnomad NFE

AF:

0.581

Gnomad OTH

AF:

0.569

GnomAD4 exome

AF:

0.568

AC:

570417

AN:

1003488

Hom.:

165087

AF XY:

0.573

AC XY:

297351

AN XY:

519060

show subpopulations

African (AFR)

AF:

0.674

AC:

16435

AN:

24374

American (AMR)

AF:

0.341

AC:

14799

AN:

43354

Ashkenazi Jewish (ASJ)

AF:

0.583

AC:

13339

AN:

22880

East Asian (EAS)

AF:

0.441

AC:

16541

AN:

37466

South Asian (SAS)

AF:

0.645

AC:

48921

AN:

75902

European-Finnish (FIN)

AF:

0.550

AC:

28776

AN:

52322

Middle Eastern (MID)

AF:

0.544

AC:

1761

AN:

3240

European-Non Finnish (NFE)

AF:

0.579

AC:

404591

AN:

698950

Other (OTH)

AF:

0.561

AC:

25254

AN:

45000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

12213

24426

36640

48853

61066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8752

17504

26256

35008

43760

<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:

0.585

AC:

88867

AN:

151928

Hom.:

26644

Cov.:

AF XY:

0.582

AC XY:

43225

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.667

AC:

27663

AN:

41454

American (AMR)

AF:

0.447

AC:

6823

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.576

AC:

1997

AN:

3468

East Asian (EAS)

AF:

0.407

AC:

2096

AN:

5150

South Asian (SAS)

AF:

0.641

AC:

3084

AN:

4812

European-Finnish (FIN)

AF:

0.550

AC:

5796

AN:

10538

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.581

AC:

39447

AN:

67932

Other (OTH)

AF:

0.572

AC:

1207

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1833

3666

5500

7333

9166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<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:

0.588

Hom.:

3305

Bravo

AF:

0.577

Asia WGS

AF:

0.538

AC:

1872

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.5

(source)

DANN

Benign

0.32

PhyloP100

-0.28

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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