rs1058932

Variant names:

• chr10-95037104-G-A
• rs1058932
• NM_000770.3:c.*24C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 39 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=-0.92).
• 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 rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.*24C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.*24C>T		3_prime_UTR_variant	Exon 9 of 9		NP_001185782.1
CYP2C8	NM_001198855.1	c.*24C>T		3_prime_UTR_variant	Exon 10 of 10		NP_001185784.1
CYP2C8	NM_001198854.1	c.*24C>T		3_prime_UTR_variant	Exon 8 of 8		NP_001185783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.*24C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_000770.3	ENSP00000360317.3

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

GnomAD2 exomes AF: 0.223 AC: 55864 AN: 250608 AF XY: 0.227

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 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

African (AFR) AF: 0.359 AC: 11964 AN: 33346

American (AMR) AF: 0.136 AC: 6085 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 5567 AN: 26080

East Asian (EAS) AF: 0.416 AC: 16488 AN: 39654

South Asian (SAS) AF: 0.330 AC: 28374 AN: 86088

European-Finnish (FIN) AF: 0.187 AC: 9990 AN: 53380

Middle Eastern (MID) AF: 0.194 AC: 1110 AN: 5734

European-Non Finnish (NFE) AF: 0.186 AC: 205701 AN: 1107476

Other (OTH) AF: 0.219 AC: 13191 AN: 60190

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

African (AFR) AF: 0.348 AC: 14397 AN: 41340

American (AMR) AF: 0.176 AC: 2683 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3464

East Asian (EAS) AF: 0.392 AC: 2026 AN: 5170

South Asian (SAS) AF: 0.335 AC: 1614 AN: 4818

European-Finnish (FIN) AF: 0.195 AC: 2063 AN: 10580

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12673 AN: 67966

Other (OTH) AF: 0.238 AC: 502 AN: 2110

Alfa AF: 0.209 Hom.: 15061

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
PhyloP100		-1.2
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: rs1058932; hg19: chr10-96796861; COSMIC: COSV64876199; COSMIC: COSV64876199;