10-95041116-T-C

Position:

• chr10-95041116-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.1149+1774A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,046 control chromosomes in the GnomAD database, including 5,478 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 (5478 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.1149+1774A>G		intron_variant		ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.939+1774A>G		intron_variant			NP_001185782.1
CYP2C8	NM_001198854.1	c.843+1774A>G		intron_variant			NP_001185783.1
CYP2C8	NM_001198855.1	c.939+1774A>G		intron_variant			NP_001185784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.1149+1774A>G		intron_variant		1	NM_000770.3	ENSP00000360317	P1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39942 AN: 151928 Hom.: 5463 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0375

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.263 AC: 39984 AN: 152046 Hom.: 5478 Cov.: 32 AF XY: 0.257 AC XY: 19107 AN XY: 74326

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.0376

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.237

Alfa AF: 0.275 Hom.: 5723

Bravo AF: 0.256

Asia WGS AF: 0.159 AC: 551 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.65

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: rs1341164; hg19: chr10-96800873;