rs1058932

Positions:

• chr10-95037104-G-A
• chr10-95037104-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000770.3(CYP2C8):​c.*24C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,608,544 control chromosomes in the GnomAD database, including 38,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.24 (4982 hom., cov: 32)
  • Exomes 𝑓: 0.20 (33607 hom.)
• Consequence: CYP2C8 NM_000770.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-95037104-G-A is Benign according to our data. Variant chr10-95037104-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.*24C>T		3_prime_UTR_variant	9/9	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.*24C>T		3_prime_UTR_variant	9/9		NP_001185782.1
CYP2C8	NM_001198854.1	c.*24C>T		3_prime_UTR_variant	8/8		NP_001185783.1
CYP2C8	NM_001198855.1	c.*24C>T		3_prime_UTR_variant	10/10		NP_001185784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.*24C>T		3_prime_UTR_variant	9/9	1	NM_000770.3	ENSP00000360317	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36871 AN: 151816 Hom.: 4966 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.231

GnomAD3 exomes AF: 0.223 AC: 55864 AN: 250608 Hom.: 7168 AF XY: 0.227 AC XY: 30682 AN XY: 135420

Gnomad AFR exome AF: 0.355

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.212

Gnomad EAS exome AF: 0.387

Gnomad SAS exome AF: 0.330

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.205 AC: 298470 AN: 1456610 Hom.: 33607 Cov.: 30 AF XY: 0.208 AC XY: 151038 AN XY: 724964

Gnomad4 AFR exome AF: 0.359

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.416

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.243 AC: 36914 AN: 151934 Hom.: 4982 Cov.: 32 AF XY: 0.245 AC XY: 18203 AN XY: 74298

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.238

Alfa AF: 0.202 Hom.: 6567

Bravo AF: 0.244

Asia WGS AF: 0.365 AC: 1265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.33

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: rs1058932; hg19: chr10-96796861; COSMIC: COSV64876199; COSMIC: COSV64876199;