rs11572169

Positions:

• chr10-95040017-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000770.3(CYP2C8):​c.1150-979A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0798 in 152,200 control chromosomes in the GnomAD database, including 609 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 (609 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.1150-979A>G		intron_variant		ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.940-979A>G		intron_variant			NP_001185782.1
CYP2C8	NM_001198854.1	c.844-979A>G		intron_variant			NP_001185783.1
CYP2C8	NM_001198855.1	c.940-979A>G		intron_variant			NP_001185784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.1150-979A>G		intron_variant		1	NM_000770.3	ENSP00000360317	P1

Frequencies

GnomAD3 genomes AF: 0.0799 AC: 12152 AN: 152082 Hom.: 609 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0926

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0377

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0798 AC: 12148 AN: 152200 Hom.: 609 Cov.: 32 AF XY: 0.0793 AC XY: 5897 AN XY: 74410

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.0924

Gnomad4 ASJ AF: 0.0914

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0377

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.104

Alfa AF: 0.112 Hom.: 1014

Bravo AF: 0.0778

Asia WGS AF: 0.0150 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.83

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: rs11572169; hg19: chr10-96799774;