rs1058930

chr10-95058362-G-Achr10-95058362-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_000770.3(CYP2C8):c.792C>T(p.Ile264=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,613,278 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: CYP2C8 NM_000770.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.579 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C8	NM_000770.3	c.792C>T	p.Ile264=	synonymous_variant	5/9	ENST00000371270.6
CYP2C8	NM_001198853.1	c.582C>T	p.Ile194=	synonymous_variant	5/9
CYP2C8	NM_001198855.1	c.582C>T	p.Ile194=	synonymous_variant	6/10
CYP2C8	NM_001198854.1	c.486C>T	p.Ile162=	synonymous_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C8	ENST00000371270.6	c.792C>T	p.Ile264=	synonymous_variant	5/9	1	NM_000770.3	P1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152062 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000996 AC: 25 AN: 251022 Hom.: 0 AF XY: 0.0000885 AC XY: 12 AN XY: 135658

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000164 AC: 240 AN: 1461098 Hom.: 0 Cov.: 31 AF XY: 0.000146 AC XY: 106 AN XY: 726854

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.000202

Gnomad4 OTH exome AF: 0.0000828

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74412

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000208 Hom.: 106

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	0.43
Dann	Benign	0.48

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

Other links and lift over

dbSNP: rs1058930; hg19: chr10-96818119; COSMIC: COSV64878317;