rs1934951

Positions:

• chr10-95038791-C-T

Variant summary

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

The ENST00000371270.6(CYP2C8):​c.1291+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,058,968 control chromosomes in the GnomAD database, including 27,445 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 (4972 hom., cov: 32)
  • Exomes 𝑓: 0.21 (22473 hom.)
• Consequence: CYP2C8 ENST00000371270.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70

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=-0.89).
• BP6: Variant 10-95038791-C-T is Benign according to our data. Variant chr10-95038791-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.1291+106G>A		intron_variant		ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.1081+106G>A		intron_variant			NP_001185782.1
CYP2C8	NM_001198854.1	c.985+106G>A		intron_variant			NP_001185783.1
CYP2C8	NM_001198855.1	c.1081+106G>A		intron_variant			NP_001185784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.1291+106G>A		intron_variant		1	NM_000770.3	ENSP00000360317	P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36807 AN: 151918 Hom.: 4956 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.211 AC: 191536 AN: 906932 Hom.: 22473 AF XY: 0.216 AC XY: 101664 AN XY: 471698

Gnomad4 AFR exome AF: 0.354

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.419

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.242 AC: 36850 AN: 152036 Hom.: 4972 Cov.: 32 AF XY: 0.244 AC XY: 18168 AN XY: 74322

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.237

Alfa AF: 0.202 Hom.: 6575

Bravo AF: 0.243

Asia WGS AF: 0.364 AC: 1264 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	0.48
DANN	Benign	0.48

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: rs1934951; hg19: chr10-96798548; COSMIC: COSV64876393; COSMIC: COSV64876393;