rs11572081

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000770.3(CYP2C8):c.480G>C(p.Lys160Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K160K) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CYP2C8
NM_000770.3 missense, splice_region

Scores

Splicing: ADA: 0.0003657

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -8.39

Publications

12 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27020732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3 link	c.480G>C	p.Lys160Asn	missense_variant, splice_region_variant	Exon 3 of 9	ENST00000371270.6	NP_000761.3	P10632-1
CYP2C8	NM_001198853.1 link	c.270G>C	p.Lys90Asn	missense_variant, splice_region_variant	Exon 3 of 9		NP_001185782.1	P10632B7Z1F5
CYP2C8	NM_001198855.1 link	c.270G>C	p.Lys90Asn	missense_variant, splice_region_variant	Exon 4 of 10		NP_001185784.1	P10632B7Z1F5
CYP2C8	NM_001198854.1 link	c.174G>C	p.Lys58Asn	missense_variant, splice_region_variant	Exon 2 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.480G>C	p.Lys160Asn	missense_variant, splice_region_variant	Exon 3 of 9	1	NM_000770.3	ENSP00000360317.3		P10632-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251402

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461780

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111938

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.017

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.029

.;.;.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.48

.;T;T;T;T

M_CAP

Benign

0.00083

MetaRNN

Benign

0.27

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.025

.;.;.;N;.

PhyloP100

-8.4

PrimateAI

Benign

0.32

PROVEAN

Benign

1.6

.;N;.;N;.

REVEL

Benign

0.039

Sift

Benign

0.76

.;T;.;T;.

Sift4G

Benign

0.51

T;T;T;T;T

Polyphen

0.0020

.;.;.;B;.

Vest4

0.067

MutPred

0.37

.;.;.;Loss of ubiquitination at K160 (P = 0.0192);.;

MVP

0.23

MPC

0.022

ClinPred

0.040

GERP RS

-7.5

PromoterAI

0.050

Neutral

(source)

Varity_R

0.10

gMVP

0.18

Mutation Taster

=53/47

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00037

dbscSNV1_RF

Benign

0.16

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over