Genetic Variant CYP2C8:c.642+151G>A (chr10-95064649-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.642+151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 768,670 control chromosomes in the GnomAD database, including 27,279 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5458 hom., cov: 32)

Exomes 𝑓: 0.26 ( 21821 hom. )

Consequence

CYP2C8
NM_000770.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Publications

8 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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000770.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYP2C8	NM_000770.3	MANE Select	c.642+151G>A	intron	N/A	NP_000761.3	P10632-1
CYP2C8	NM_001198853.1		c.432+151G>A	intron	N/A	NP_001185782.1	P10632
CYP2C8	NM_001198855.1		c.432+151G>A	intron	N/A	NP_001185784.1	P10632

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYP2C8	ENST00000371270.6	TSL:1 MANE Select	c.642+151G>A	intron	N/A	ENSP00000360317.3	P10632-1
CYP2C8	ENST00000854622.1		c.642+151G>A	intron	N/A	ENSP00000524681.1
CYP2C8	ENST00000854631.1		c.642+151G>A	intron	N/A	ENSP00000524690.1

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39860

AN:

151960

Hom.:

5446

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.0379

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.290

Gnomad OTH

AF:

0.240

GnomAD4 exome

AF:

0.256

AC:

157805

AN:

616592

Hom.:

21821

AF XY:

0.255

AC XY:

82307

AN XY:

322380

show subpopulations

African (AFR)

AF:

0.281

AC:

4165

AN:

14802

American (AMR)

AF:

0.155

AC:

3159

AN:

20372

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

3590

AN:

15818

East Asian (EAS)

AF:

0.0339

AC:

1035

AN:

30564

South Asian (SAS)

AF:

0.217

AC:

10547

AN:

48500

European-Finnish (FIN)

AF:

0.271

AC:

9733

AN:

35888

Middle Eastern (MID)

AF:

0.238

AC:

543

AN:

2284

European-Non Finnish (NFE)

AF:

0.281

AC:

117445

AN:

417496

Other (OTH)

AF:

0.246

AC:

7588

AN:

30868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5404

10808

16212

21616

27020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2090

4180

6270

8360

10450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.262

AC:

39895

AN:

152078

Hom.:

5458

Cov.:

AF XY:

0.257

AC XY:

19071

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.282

AC:

11699

AN:

41488

American (AMR)

AF:

0.180

AC:

2755

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

808

AN:

3470

East Asian (EAS)

AF:

0.0380

AC:

197

AN:

5182

South Asian (SAS)

AF:

0.217

AC:

1047

AN:

4822

European-Finnish (FIN)

AF:

0.264

AC:

2786

AN:

10562

Middle Eastern (MID)

AF:

0.233

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.290

AC:

19735

AN:

67974

Other (OTH)

AF:

0.238

AC:

502

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1531

3061

4592

6122

7653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.272

Hom.:

17433

Bravo

AF:

0.255

Asia WGS

AF:

0.160

AC:

555

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.6

(source)

DANN

Benign

0.25

PhyloP100

-1.1

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over