10-95064649-C-T

Variant names:

• chr10-95064649-C-T
• rs11572093
• NM_000770.3:c.642+151G>A

Variant summary

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

The NM_000770.3(CYP2C8):​c.642+151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 768,670 control chromosomes in the GnomAD database, including 27,279 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 (5458 hom., cov: 32)
  • Exomes 𝑓: 0.26 (21821 hom.)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.93).
• 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 rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.642+151G>A		intron_variant	Intron 4 of 8	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.432+151G>A		intron_variant	Intron 4 of 8		NP_001185782.1
CYP2C8	NM_001198855.1	c.432+151G>A		intron_variant	Intron 5 of 9		NP_001185784.1
CYP2C8	NM_001198854.1	c.336+151G>A		intron_variant	Intron 3 of 7		NP_001185783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.642+151G>A		intron_variant	Intron 4 of 8	1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39860 AN: 151960 Hom.: 5446 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0379

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.256 AC: 157805 AN: 616592 Hom.: 21821 AF XY: 0.255 AC XY: 82307 AN XY: 322380

Gnomad4 AFR exome AF: 0.281

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.0339

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.262 AC: 39895 AN: 152078 Hom.: 5458 Cov.: 32 AF XY: 0.257 AC XY: 19071 AN XY: 74330

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.0380

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.238

Alfa AF: 0.268 Hom.: 8831

Bravo AF: 0.255

Asia WGS AF: 0.160 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.25

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: rs11572093; hg19: chr10-96824406;