dbSNP rs11572082: CYP2C8:c.481+43G>C (chr10-95067165-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000770.3(CYP2C8):c.481+43G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,612,770 control chromosomes in the GnomAD database, including 9,713 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 0.080 ( 610 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9103 hom. )

Consequence

CYP2C8
NM_000770.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.888

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3 link	c.481+43G>C	intron_variant	Intron 3 of 8	ENST00000371270.6	NP_000761.3	P10632-1
CYP2C8	NM_001198853.1 link	c.271+43G>C	intron_variant	Intron 3 of 8		NP_001185782.1	P10632B7Z1F5
CYP2C8	NM_001198855.1 link	c.271+43G>C	intron_variant	Intron 4 of 9		NP_001185784.1	P10632B7Z1F5
CYP2C8	NM_001198854.1 link	c.175+43G>C	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.481+43G>C		intron_variant	Intron 3 of 8	1	NM_000770.3	ENSP00000360317.3		P10632-1

Frequencies

GnomAD3 genomes

AF:

0.0798

AC:

12140

AN:

152070

Hom.:

610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0212

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.0925

Gnomad ASJ

AF:

0.0912

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0380

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.0833

AC:

20888

AN:

250850

Hom.:

1115

AF XY:

0.0848

AC XY:

11504

AN XY:

135586

show subpopulations

Gnomad AFR exome

AF:

0.0202

Gnomad AMR exome

AF:

0.0675

Gnomad ASJ exome

AF:

0.0990

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0408

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.106

AC:

154184

AN:

1460582

Hom.:

9103

Cov.:

AF XY:

0.104

AC XY:

75643

AN XY:

726666

show subpopulations

Gnomad4 AFR exome

AF:

0.0185

Gnomad4 AMR exome

AF:

0.0716

Gnomad4 ASJ exome

AF:

0.0956

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0431

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.119

Gnomad4 OTH exome

AF:

0.0961

GnomAD4 genome

AF:

0.0797

AC:

12136

AN:

152188

Hom.:

610

Cov.:

AF XY:

0.0791

AC XY:

5885

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0211

Gnomad4 AMR

AF:

0.0923

Gnomad4 ASJ

AF:

0.0912

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0380

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.0509

Hom.:

Bravo

AF:

0.0777

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.80

DANN

Benign

0.43

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over