Variant 10-95067209-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_000770.3(CYP2C8):c.480G>A(p.Lys160=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00866 in 1,613,980 control chromosomes in the GnomAD database, including 1,023 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.045 ( 569 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 454 hom. )

Consequence

CYP2C8
NM_000770.3 splice_region, synonymous

Scores

Splicing: ADA: 0.0005856

Clinical Significance

Benign no assertion criteria provided B:1

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 10-95067209-C-T is Benign according to our data. Variant chr10-95067209-C-T is described in ClinVar as [Benign]. Clinvar id is 3056915.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-95067209-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-8.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CYP2C8	NM_000770.3 linkuse as main transcript	c.480G>A	p.Lys160=	splice_region_variant, synonymous_variant	3/9	ENST00000371270.6
CYP2C8	NM_001198853.1 linkuse as main transcript	c.270G>A	p.Lys90=	splice_region_variant, synonymous_variant	3/9
CYP2C8	NM_001198855.1 linkuse as main transcript	c.270G>A	p.Lys90=	splice_region_variant, synonymous_variant	4/10
CYP2C8	NM_001198854.1 linkuse as main transcript	c.174G>A	p.Lys58=	splice_region_variant, synonymous_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C8	ENST00000371270.6 linkuse as main transcript	c.480G>A	p.Lys160=	splice_region_variant, synonymous_variant	3/9	1	NM_000770.3	P1	P10632-1

Frequencies

GnomAD3 genomes

AF:

0.0446

AC:

6784

AN:

152084

Hom.:

567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0195

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.0307

GnomAD3 exomes

AF:

0.0119

AC:

2993

AN:

251402

Hom.:

189

AF XY:

0.00881

AC XY:

1197

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.00821

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000721

Gnomad OTH exome

AF:

0.00929

GnomAD4 exome

AF:

0.00492

AC:

7192

AN:

1461778

Hom.:

454

Cov.:

AF XY:

0.00426

AC XY:

3099

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.00950

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000561

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.0446

AC:

6791

AN:

152202

Hom.:

569

Cov.:

AF XY:

0.0427

AC XY:

3178

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.0195

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000765

Gnomad4 OTH

AF:

0.0304

Alfa

AF:

0.00903

Hom.:

164

Bravo

AF:

0.0512

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CYP2C8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 26, 2020

This variant is classified as 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

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.49

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00059

dbscSNV1_RF

Benign

0.13

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