Variant chr10-95042946-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_000770.3(CYP2C8):c.1093G>A(p.Gly365Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,614,070 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

CYP2C8
NM_000770.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.134

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015227944).

BP6

Variant 10-95042946-C-T is Benign according to our data. Variant chr10-95042946-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3049531.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C8	NM_000770.3 link	c.1093G>A	p.Gly365Ser	missense_variant	7/9	ENST00000371270.6	NP_000761.3	P10632-1
CYP2C8	NM_001198853.1 link	c.883G>A	p.Gly295Ser	missense_variant	7/9		NP_001185782.1	P10632B7Z1F5
CYP2C8	NM_001198855.1 link	c.883G>A	p.Gly295Ser	missense_variant	8/10		NP_001185784.1	P10632B7Z1F5
CYP2C8	NM_001198854.1 link	c.787G>A	p.Gly263Ser	missense_variant	6/8		NP_001185783.1	P10632-2B7Z1F5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6 link	c.1093G>A	p.Gly365Ser	missense_variant	7/9	1	NM_000770.3	ENSP00000360317.3		P10632-1

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

197

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000477

AC:

120

AN:

251466

Hom.:

AF XY:

0.000383

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00584

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000185

AC:

271

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000182

AC XY:

132

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00451

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000531

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.00129

AC:

197

AN:

152222

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00431

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000267

Hom.:

Bravo

AF:

0.00150

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000618

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CYP2C8-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 04, 2019

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.71

DANN

Benign

0.41

DEOGEN2

Benign

0.032

.;.;.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.75

.;T;T;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.015

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.085

.;.;.;N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

1.3

.;N;.;N;.

REVEL

Benign

0.061

Sift

Benign

0.58

.;T;.;T;.

Sift4G

Benign

0.53

T;T;T;T;T

Polyphen

0.017

.;.;.;B;.

Vest4

0.043

MVP

0.40

MPC

0.023

ClinPred

0.0016

GERP RS

2.0

Varity_R

0.11

gMVP

0.12

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