10-95065218-C-T

Variant names:

• chr10-95065218-C-T
• rs2185571
• NM_000770.3:c.482-258G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000770.3(CYP2C8):​c.482-258G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,030 control chromosomes in the GnomAD database, including 4,056 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 0.22 (4056 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.482-258G>A		intron_variant	Intron 3 of 8	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.272-258G>A		intron_variant	Intron 3 of 8		NP_001185782.1
CYP2C8	NM_001198855.1	c.272-258G>A		intron_variant	Intron 4 of 9		NP_001185784.1
CYP2C8	NM_001198854.1	c.176-258G>A		intron_variant	Intron 2 of 7		NP_001185783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.482-258G>A		intron_variant	Intron 3 of 8	1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33042 AN: 151912 Hom.: 4052 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0374

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.218 AC: 33070 AN: 152030 Hom.: 4056 Cov.: 32 AF XY: 0.214 AC XY: 15880 AN XY: 74286

African (AFR) AF: 0.128 AC: 5307 AN: 41494

American (AMR) AF: 0.161 AC: 2462 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 808 AN: 3472

East Asian (EAS) AF: 0.0375 AC: 194 AN: 5180

South Asian (SAS) AF: 0.217 AC: 1046 AN: 4814

European-Finnish (FIN) AF: 0.265 AC: 2791 AN: 10528

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19668 AN: 67952

Other (OTH) AF: 0.206 AC: 435 AN: 2112

Alfa AF: 0.260 Hom.: 7879

Bravo AF: 0.204

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.50
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2185571; hg19: chr10-96824975;