10-95058349-T-A

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.805A>T(p.Ile269Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,613,126 control chromosomes in the GnomAD database, including 1,010 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.046 ( 516 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 494 hom. )

Consequence

CYP2C8
NM_000770.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.91

Publications

120 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=0.0019989312).

BP6

Variant 10-95058349-T-A is Benign according to our data. Variant chr10-95058349-T-A is described in ClinVar as [Benign]. Clinvar id is 545586.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3 link	c.805A>T	p.Ile269Phe	missense_variant	Exon 5 of 9	ENST00000371270.6	NP_000761.3	P10632-1
CYP2C8	NM_001198853.1 link	c.595A>T	p.Ile199Phe	missense_variant	Exon 5 of 9		NP_001185782.1	P10632B7Z1F5
CYP2C8	NM_001198855.1 link	c.595A>T	p.Ile199Phe	missense_variant	Exon 6 of 10		NP_001185784.1	P10632B7Z1F5
CYP2C8	NM_001198854.1 link	c.499A>T	p.Ile167Phe	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.805A>T	p.Ile269Phe	missense_variant	Exon 5 of 9	1	NM_000770.3	ENSP00000360317.3		P10632-1

Frequencies

GnomAD3 genomes

AF:

0.0460

AC:

7001

AN:

152100

Hom.:

513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00282

Gnomad OTH

AF:

0.0416

GnomAD2 exomes

AF:

0.0158

AC:

3975

AN:

251032

AF XY:

0.0136

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.00836

Gnomad ASJ exome

AF:

0.0141

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00314

Gnomad OTH exome

AF:

0.00998

GnomAD4 exome

AF:

0.00759

AC:

11092

AN:

1460908

Hom.:

494

Cov.:

AF XY:

0.00753

AC XY:

5472

AN XY:

726760

show subpopulations

African (AFR)

AF:

0.159

AC:

5325

AN:

33424

American (AMR)

AF:

0.00986

AC:

440

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.0149

AC:

390

AN:

26102

East Asian (EAS)

AF:

0.000101

AC:

AN:

39622

South Asian (SAS)

AF:

0.0203

AC:

1752

AN:

86240

European-Finnish (FIN)

AF:

0.000206

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.0233

AC:

132

AN:

5670

European-Non Finnish (NFE)

AF:

0.00196

AC:

2175

AN:

1111482

Other (OTH)

AF:

0.0143

AC:

863

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

590

1181

1771

2362

2952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0462

AC:

7025

AN:

152218

Hom.:

516

Cov.:

AF XY:

0.0450

AC XY:

3352

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.153

AC:

6336

AN:

41512

American (AMR)

AF:

0.0164

AC:

250

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.0197

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00282

AC:

192

AN:

68014

Other (OTH)

AF:

0.0412

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

303

606

910

1213

1516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00633

Hom.:

Bravo

AF:

0.0527

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.157

AC:

690

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.0194

AC:

2350

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.00387

EpiControl

AF:

0.00474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

0.29

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.26

.;.;.;T;.

Eigen

Benign

0.18

Eigen_PC

Benign

0.087

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.93

.;D;D;D;D

MetaRNN

Benign

0.0020

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Pathogenic

3.3

.;.;.;M;.

PhyloP100

1.9

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.9

.;D;.;D;.

REVEL

Benign

0.28

Sift

Uncertain

0.0060

.;D;.;D;.

Sift4G

Uncertain

0.0030

D;D;D;D;D

Polyphen

0.96

.;.;.;D;.

Vest4

0.14

MPC

0.18

ClinPred

0.053

GERP RS

4.2

Varity_R

0.74

gMVP

0.16

Mutation Taster

=38/62

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.

10-95058349-T-A

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