dbSNP rs3752988: CYP2C8:c.482-166A>G (chr10-95065126-T-C) – 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.482-166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,074 control chromosomes in the GnomAD database, including 11,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.38 ( 11253 hom., cov: 33)

Consequence

CYP2C8
NM_000770.3 intron

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: -2.17

Publications

6 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:

Genome browser will be placed here

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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3 link	c.482-166A>G	intron_variant	Intron 3 of 8	ENST00000371270.6	NP_000761.3	P10632-1
CYP2C8	NM_001198853.1 link	c.272-166A>G	intron_variant	Intron 3 of 8		NP_001185782.1	P10632B7Z1F5
CYP2C8	NM_001198855.1 link	c.272-166A>G	intron_variant	Intron 4 of 9		NP_001185784.1	P10632B7Z1F5
CYP2C8	NM_001198854.1 link	c.176-166A>G	intron_variant	Intron 2 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.482-166A>G		intron_variant	Intron 3 of 8	1	NM_000770.3	ENSP00000360317.3		P10632-1

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57425

AN:

151956

Hom.:

11237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.415

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.413

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

GnomAD4 genome

AF:

0.378

AC:

57476

AN:

152074

Hom.:

11253

Cov.:

AF XY:

0.378

AC XY:

28104

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.476

AC:

19741

AN:

41468

American (AMR)

AF:

0.321

AC:

4902

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.415

AC:

1438

AN:

3468

East Asian (EAS)

AF:

0.394

AC:

2042

AN:

5178

South Asian (SAS)

AF:

0.400

AC:

1928

AN:

4822

European-Finnish (FIN)

AF:

0.318

AC:

3356

AN:

10562

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22668

AN:

67980

Other (OTH)

AF:

0.416

AC:

880

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1798

3596

5395

7193

8991

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.362

Hom.:

19371

Bravo

AF:

0.382

Asia WGS

AF:

0.400

AC:

1390

AN:

3474

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

-0.87

CADD

Benign

0.69

(source)

DANN

Benign

0.72

PhyloP100

-2.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over