Variant 10-95058349-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

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 no assertion criteria provided B:1

Conservation

PhyloP100: 1.91

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019989312).

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/exons	MANE
CYP2C8	NM_000770.3 linkuse as main transcript	c.805A>T	p.Ile269Phe	missense_variant	5/9	ENST00000371270.6
CYP2C8	NM_001198853.1 linkuse as main transcript	c.595A>T	p.Ile199Phe	missense_variant	5/9
CYP2C8	NM_001198855.1 linkuse as main transcript	c.595A>T	p.Ile199Phe	missense_variant	6/10
CYP2C8	NM_001198854.1 linkuse as main transcript	c.499A>T	p.Ile167Phe	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C8	ENST00000371270.6 linkuse as main transcript	c.805A>T	p.Ile269Phe	missense_variant	5/9	1	NM_000770.3	P1	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

GnomAD3 exomes

AF:

0.0158

AC:

3975

AN:

251032

Hom.:

208

AF XY:

0.0136

AC XY:

1849

AN XY:

135672

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 SAS exome

AF:

0.0195

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

Gnomad4 AFR exome

AF:

0.159

Gnomad4 AMR exome

AF:

0.00986

Gnomad4 ASJ exome

AF:

0.0149

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0203

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00196

Gnomad4 OTH exome

AF:

0.0143

GnomAD4 genome

AF:

0.0462

AC:

7025

AN:

152218

Hom.:

516

Cov.:

AF XY:

0.0450

AC XY:

3352

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.0164

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0197

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00282

Gnomad4 OTH

AF:

0.0412

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:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CYP2C8 POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jun 20, 2018

- -

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

Dann

Uncertain

0.98

Eigen

Benign

0.18

Eigen_PC

Benign

0.087

FATHMM_MKL

Uncertain

0.82

MetaRNN

Benign

0.0020

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

0.0035

P;P;P

PrimateAI

Benign

0.37

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over