Variant 10-95067362-TA-TAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000770.3(CYP2C8):c.332-6dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,613,462 control chromosomes in the GnomAD database, including 52,419 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7548 hom., cov: 19)

Exomes 𝑓: 0.24 ( 44871 hom. )

Consequence

CYP2C8
NM_000770.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.927

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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CYP2C8	NM_000770.3 link	c.332-6dupT	splice_region_variant, intron_variant	ENST00000371270.6	NP_000761.3	P10632-1
CYP2C8	NM_001198853.1 link	c.122-6dupT	splice_region_variant, intron_variant		NP_001185782.1	P10632B7Z1F5
CYP2C8	NM_001198855.1 link	c.122-6dupT	splice_region_variant, intron_variant		NP_001185784.1	P10632B7Z1F5
CYP2C8	NM_001198854.1 link	c.26-6dupT	splice_region_variant, intron_variant		NP_001185783.1	P10632-2B7Z1F5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6 link	c.332-6dupT		splice_region_variant, intron_variant		1	NM_000770.3	ENSP00000360317.3		P10632-1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45014

AN:

151624

Hom.:

7529

Cov.:

show subpopulations

Gnomad AFR

AF:

0.451

Gnomad AMI

AF:

0.256

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.392

Gnomad SAS

AF:

0.361

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.307

GnomAD3 exomes

AF:

0.261

AC:

65413

AN:

250816

Hom.:

9644

AF XY:

0.264

AC XY:

35764

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.454

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.340

Gnomad EAS exome

AF:

0.387

Gnomad SAS exome

AF:

0.356

Gnomad FIN exome

AF:

0.202

Gnomad NFE exome

AF:

0.220

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.238

AC:

348286

AN:

1461718

Hom.:

44871

Cov.:

AF XY:

0.242

AC XY:

175777

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.463

Gnomad4 AMR exome

AF:

0.174

Gnomad4 ASJ exome

AF:

0.337

Gnomad4 EAS exome

AF:

0.416

Gnomad4 SAS exome

AF:

0.356

Gnomad4 FIN exome

AF:

0.201

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.266

GnomAD4 genome

AF:

0.297

AC:

45068

AN:

151744

Hom.:

7548

Cov.:

AF XY:

0.297

AC XY:

22049

AN XY:

74118

show subpopulations

Gnomad4 AFR

AF:

0.451

Gnomad4 AMR

AF:

0.228

Gnomad4 ASJ

AF:

0.324

Gnomad4 EAS

AF:

0.392

Gnomad4 SAS

AF:

0.361

Gnomad4 FIN

AF:

0.204

Gnomad4 NFE

AF:

0.220

Gnomad4 OTH

AF:

0.311

Alfa

AF:

0.171

Hom.:

469

EpiCase

AF:

0.233

EpiControl

AF:

0.238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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