10-95039038-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PP3BP6_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

Publications

9 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: Likely_benign. The variant received -5 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

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 rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3 link	c.1150G>A	p.Gly384Ser	missense_variant, splice_region_variant	Exon 8 of 9	ENST00000371270.6	NP_000761.3	P10632-1
CYP2C8	NM_001198853.1 link	c.940G>A	p.Gly314Ser	missense_variant, splice_region_variant	Exon 8 of 9		NP_001185782.1	P10632B7Z1F5
CYP2C8	NM_001198855.1 link	c.940G>A	p.Gly314Ser	missense_variant, splice_region_variant	Exon 9 of 10		NP_001185784.1	P10632B7Z1F5
CYP2C8	NM_001198854.1 link	c.844G>A	p.Gly282Ser	missense_variant, splice_region_variant	Exon 7 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.1150G>A	p.Gly384Ser	missense_variant, splice_region_variant	Exon 8 of 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

GnomAD2 exomes

AF:

0.000955

AC:

240

AN:

251394

AF XY:

0.00114

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 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

African (AFR)

AF:

0.000329

AC:

AN:

33454

American (AMR)

AF:

0.000827

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000574

AC:

AN:

26126

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39688

South Asian (SAS)

AF:

0.00262

AC:

226

AN:

86240

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00143

AC:

1587

AN:

1111136

Other (OTH)

AF:

0.00149

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

193

290

386

483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000729

AC:

111

AN:

152202

Hom.:

Cov.:

AF XY:

0.000726

AC XY:

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41522

American (AMR)

AF:

0.000589

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00290

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00104

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00101

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

Jul 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

7.0

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

Mutation Taster

=94/6

polymorphism

(source)

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

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10-95039038-C-T

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