Genetic Variant CYP2C8:c.1292-404G>A (chr10-95037713-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000770.3(CYP2C8):c.1292-404G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,040 control chromosomes in the GnomAD database, including 36,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.69 ( 36575 hom., cov: 32)

Consequence

CYP2C8
NM_000770.3 intron

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: -1.88

Publications

14 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3 link	c.1292-404G>A	intron_variant	Intron 8 of 8	ENST00000371270.6	NP_000761.3	P10632-1
CYP2C8	NM_001198853.1 link	c.1082-404G>A	intron_variant	Intron 8 of 8		NP_001185782.1	P10632B7Z1F5
CYP2C8	NM_001198855.1 link	c.1082-404G>A	intron_variant	Intron 9 of 9		NP_001185784.1	P10632B7Z1F5
CYP2C8	NM_001198854.1 link	c.986-404G>A	intron_variant	Intron 7 of 7		NP_001185783.1	P10632-2B7Z1F5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6 link	c.1292-404G>A		intron_variant	Intron 8 of 8	1	NM_000770.3	ENSP00000360317.3		P10632-1

Frequencies

GnomAD3 genomes

AF:

0.687

AC:

104304

AN:

151922

Hom.:

36523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.807

Gnomad AMI

AF:

0.738

Gnomad AMR

AF:

0.558

Gnomad ASJ

AF:

0.706

Gnomad EAS

AF:

0.461

Gnomad SAS

AF:

0.668

Gnomad FIN

AF:

0.616

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.669

Gnomad OTH

AF:

0.704

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.687

AC:

104405

AN:

152040

Hom.:

36575

Cov.:

AF XY:

0.681

AC XY:

50604

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.807

AC:

33473

AN:

41478

American (AMR)

AF:

0.557

AC:

8508

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.706

AC:

2450

AN:

3468

East Asian (EAS)

AF:

0.461

AC:

2385

AN:

5172

South Asian (SAS)

AF:

0.669

AC:

3225

AN:

4818

European-Finnish (FIN)

AF:

0.616

AC:

6495

AN:

10548

Middle Eastern (MID)

AF:

0.840

AC:

247

AN:

294

European-Non Finnish (NFE)

AF:

0.669

AC:

45458

AN:

67962

Other (OTH)

AF:

0.706

AC:

1491

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1641

3281

4922

6562

8203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.673

Hom.:

108031

Bravo

AF:

0.684

Asia WGS

AF:

0.607

AC:

2109

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to

Other:1

Jul 05, 2022

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance:association

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.13

(source)

DANN

Benign

0.20

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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10-95037713-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over