10-95049216-A-G

Variant names:

• chr10-95049216-A-G
• rs1934980
• NM_000770.3:c.820-3265T>C

Variant summary

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

The NM_000770.3(CYP2C8):​c.820-3265T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,160 control chromosomes in the GnomAD database, including 3,092 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 0.20 (3092 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688

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=-0.97).
• 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.820-3265T>C		intron_variant	Intron 5 of 8	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.610-3265T>C		intron_variant	Intron 5 of 8		NP_001185782.1
CYP2C8	NM_001198855.1	c.610-3265T>C		intron_variant	Intron 6 of 9		NP_001185784.1
CYP2C8	NM_001198854.1	c.514-3265T>C		intron_variant	Intron 4 of 7		NP_001185783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.820-3265T>C		intron_variant	Intron 5 of 8	1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29768 AN: 152042 Hom.: 3082 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.196 AC: 29787 AN: 152160 Hom.: 3092 Cov.: 32 AF XY: 0.199 AC XY: 14798 AN XY: 74392

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.195

Alfa AF: 0.187 Hom.: 2643

Bravo AF: 0.190

Asia WGS AF: 0.347 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.56

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: rs1934980; hg19: chr10-96808973;