Variant rs11572081 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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. 17/23 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

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 made for transcript

Verdict is Uncertain_significance. Variant got 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/exons	MANE
CYP2C8	NM_000770.3 linkuse as main transcript	c.480G>C	p.Lys160Asn	missense_variant, splice_region_variant	3/9	ENST00000371270.6
CYP2C8	NM_001198853.1 linkuse as main transcript	c.270G>C	p.Lys90Asn	missense_variant, splice_region_variant	3/9
CYP2C8	NM_001198855.1 linkuse as main transcript	c.270G>C	p.Lys90Asn	missense_variant, splice_region_variant	4/10
CYP2C8	NM_001198854.1 linkuse as main transcript	c.174G>C	p.Lys58Asn	missense_variant, splice_region_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C8	ENST00000371270.6 linkuse as main transcript	c.480G>C	p.Lys160Asn	missense_variant, splice_region_variant	3/9	1	NM_000770.3	P1	P10632-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251402

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135864

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 SAS 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

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

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;.

MutationTaster

Benign

0.14

P;P;P

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

Varity_R

0.10

gMVP

0.18

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over