10-95039038-C-T

Position:

chr10-95039038-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_000770.3(CYP2C8):c.1150G>A(p.Gly384Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00129 in 1,613,100 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 8 hom. )

Consequence

CYP2C8
NM_000770.3 missense, splice_region

Scores

Splicing: ADA: 0.9918

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.98

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:

CYP2C8 (HGNC:):

CYP2C8 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 10-95039038-C-T is Benign according to our data. Variant chr10-95039038-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 733649.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C8	NM_000770.3 linkuse as main transcript	c.1150G>A	p.Gly384Ser	missense_variant, splice_region_variant	8/9	ENST00000371270.6	NP_000761.3	P10632-1
CYP2C8	NM_001198853.1 linkuse as main transcript	c.940G>A	p.Gly314Ser	missense_variant, splice_region_variant	8/9		NP_001185782.1	P10632B7Z1F5
CYP2C8	NM_001198855.1 linkuse as main transcript	c.940G>A	p.Gly314Ser	missense_variant, splice_region_variant	9/10		NP_001185784.1	P10632B7Z1F5
CYP2C8	NM_001198854.1 linkuse as main transcript	c.844G>A	p.Gly282Ser	missense_variant, splice_region_variant	7/8		NP_001185783.1	P10632-2B7Z1F5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6 linkuse as main transcript	c.1150G>A	p.Gly384Ser	missense_variant, splice_region_variant	8/9	1	NM_000770.3	ENSP00000360317.3		P10632-1

Frequencies

GnomAD3 genomes

AF:

0.000730

AC:

111

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000955

AC:

240

AN:

251394

Hom.:

AF XY:

0.00114

AC XY:

155

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000810

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00265

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000985

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00135

AC:

1970

AN:

1460898

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1027

AN XY:

726848

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00262

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00143

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.000729

AC:

111

AN:

152202

Hom.:

Cov.:

AF XY:

0.000726

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000733

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000782

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.00101

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

.;.;.;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

.;D;D;D

M_CAP

Benign

0.063

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Uncertain

0.60

MutationAssessor

Pathogenic

3.7

.;.;.;H

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-4.8

.;D;.;D

REVEL

Pathogenic

0.74

Sift

Uncertain

0.012

.;D;.;D

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

0.98

.;.;.;D

Vest4

0.50

MVP

0.88

MPC

0.12

ClinPred

0.64

GERP RS

4.0

Varity_R

0.66

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.78

SpliceAI score (max)

0.030

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