10-95058362-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000770.3(CYP2C8):c.792C>G(p.Ile264Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 1,613,150 control chromosomes in the GnomAD database, including 1,876 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.035 ( 120 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1756 hom. )

Consequence

CYP2C8
NM_000770.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: -0.579

Publications

134 publications found

Variant links:

Genes affected

CYP2C8 (HGNC:2622): (cytochrome P450 family 2 subfamily C member 8) 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 phenobarbital. The enzyme is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, benzo(a)pyrene, 7-ethyoxycoumarin, and the anti-cancer drug taxol. This gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

CYP2C8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040852427).

BP6

Variant 10-95058362-G-C is Benign according to our data. Variant chr10-95058362-G-C is described in ClinVar as [Benign]. Clinvar id is 545585.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3 link	c.792C>G	p.Ile264Met	missense_variant	Exon 5 of 9	ENST00000371270.6	NP_000761.3	P10632-1
CYP2C8	NM_001198853.1 link	c.582C>G	p.Ile194Met	missense_variant	Exon 5 of 9		NP_001185782.1	P10632B7Z1F5
CYP2C8	NM_001198855.1 link	c.582C>G	p.Ile194Met	missense_variant	Exon 6 of 10		NP_001185784.1	P10632B7Z1F5
CYP2C8	NM_001198854.1 link	c.486C>G	p.Ile162Met	missense_variant	Exon 4 of 8		NP_001185783.1	P10632-2B7Z1F5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6 link	c.792C>G	p.Ile264Met	missense_variant	Exon 5 of 9	1	NM_000770.3	ENSP00000360317.3		P10632-1

Frequencies

GnomAD3 genomes

AF:

0.0355

AC:

5397

AN:

152042

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0312

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.0582

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0521

Gnomad OTH

AF:

0.0368

GnomAD2 exomes

AF:

0.0375

AC:

9410

AN:

251022

AF XY:

0.0374

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.0274

Gnomad ASJ exome

AF:

0.0184

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0568

Gnomad NFE exome

AF:

0.0543

Gnomad OTH exome

AF:

0.0427

GnomAD4 exome

AF:

0.0463

AC:

67688

AN:

1460990

Hom.:

1756

Cov.:

AF XY:

0.0456

AC XY:

33142

AN XY:

726798

show subpopulations

African (AFR)

AF:

0.00951

AC:

318

AN:

33438

American (AMR)

AF:

0.0278

AC:

1241

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.0201

AC:

524

AN:

26106

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39632

South Asian (SAS)

AF:

0.0151

AC:

1306

AN:

86242

European-Finnish (FIN)

AF:

0.0599

AC:

3198

AN:

53396

Middle Eastern (MID)

AF:

0.0187

AC:

107

AN:

5736

European-Non Finnish (NFE)

AF:

0.0526

AC:

58461

AN:

1111450

Other (OTH)

AF:

0.0419

AC:

2530

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

3628

7256

10885

14513

18141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0354

AC:

5394

AN:

152160

Hom.:

120

Cov.:

AF XY:

0.0345

AC XY:

2568

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0119

AC:

494

AN:

41558

American (AMR)

AF:

0.0310

AC:

474

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0185

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.0150

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0582

AC:

615

AN:

10566

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0521

AC:

3545

AN:

67984

Other (OTH)

AF:

0.0365

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

259

518

776

1035

1294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0400

Hom.:

106

Bravo

AF:

0.0332

TwinsUK

AF:

0.0491

AC:

182

ALSPAC

AF:

0.0483

AC:

186

ESP6500AA

AF:

0.0129

AC:

ESP6500EA

AF:

0.0548

AC:

471

ExAC

AF:

0.0386

AC:

4687

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.0480

EpiControl

AF:

0.0527

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CYP2C8-related disorder

Benign:1

Feb 07, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

CYP2C8 POLYMORPHISM

Benign:1

Jun 20, 2018

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.23

CADD

Benign

4.8

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.27

.;.;.;T;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.49

LIST_S2

Uncertain

0.86

.;D;D;D;D

MetaRNN

Benign

0.0041

T;T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Pathogenic

3.0

.;.;.;M;.

PhyloP100

-0.58

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.6

.;D;.;D;.

REVEL

Uncertain

0.36

Sift

Uncertain

0.0030

.;D;.;D;.

Sift4G

Uncertain

0.016

D;D;D;D;D

Polyphen

0.99

.;.;.;D;.

Vest4

0.29

MPC

0.18

ClinPred

0.094

GERP RS

-2.8

Varity_R

0.89

gMVP

0.21

Mutation Taster

=93/7

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.

10-95058362-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over