Variant rs11188150 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000770.3(CYP2C8):c.1059C>T(p.His353=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00553 in 1,614,018 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 191 hom. )

Consequence

CYP2C8
NM_000770.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.775

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 10-95042980-G-A is Benign according to our data. Variant chr10-95042980-G-A is described in ClinVar as [Benign]. Clinvar id is 775289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-95042980-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.775 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0037 (564/152270) while in subpopulation SAS AF= 0.0498 (240/4822). AF 95% confidence interval is 0.0446. There are 11 homozygotes in gnomad4. There are 332 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CYP2C8	NM_000770.3 linkuse as main transcript	c.1059C>T	p.His353=	synonymous_variant	7/9	ENST00000371270.6
CYP2C8	NM_001198853.1 linkuse as main transcript	c.849C>T	p.His283=	synonymous_variant	7/9
CYP2C8	NM_001198855.1 linkuse as main transcript	c.849C>T	p.His283=	synonymous_variant	8/10
CYP2C8	NM_001198854.1 linkuse as main transcript	c.753C>T	p.His251=	synonymous_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C8	ENST00000371270.6 linkuse as main transcript	c.1059C>T	p.His353=	synonymous_variant	7/9	1	NM_000770.3	P1	P10632-1

Frequencies

GnomAD3 genomes

AF:

0.00369

AC:

562

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0493

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00279

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00882

AC:

2217

AN:

251478

Hom.:

AF XY:

0.0113

AC XY:

1541

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0506

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00323

Gnomad OTH exome

AF:

0.00929

GnomAD4 exome

AF:

0.00572

AC:

8355

AN:

1461748

Hom.:

191

Cov.:

AF XY:

0.00734

AC XY:

5334

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.0176

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0502

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00254

Gnomad4 OTH exome

AF:

0.00782

GnomAD4 genome

AF:

0.00370

AC:

564

AN:

152270

Hom.:

Cov.:

AF XY:

0.00446

AC XY:

332

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0498

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00279

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00450

Hom.:

Bravo

AF:

0.00254

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.00480

EpiControl

AF:

0.00480

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.10

DANN

Benign

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

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