10-95050855-C-T

Variant names:

• chr10-95050855-C-T
• rs1341162
• NM_000770.3:c.820-4904G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000770.3(CYP2C8):​c.820-4904G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 148,616 control chromosomes in the GnomAD database, including 7,639 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 0.30 (7639 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 11 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000770.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	NM_000770.3	MANE Select	c.820-4904G>A		intron	N/A	NP_000761.3	P10632-1
	CYP2C8	NM_001198853.1		c.610-4904G>A		intron	N/A	NP_001185782.1	P10632
	CYP2C8	NM_001198855.1		c.610-4904G>A		intron	N/A	NP_001185784.1	P10632

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	ENST00000371270.6	TSL:1 MANE Select	c.820-4904G>A		intron	N/A	ENSP00000360317.3	P10632-1
	CYP2C8	ENST00000854622.1		c.820-2553G>A		intron	N/A	ENSP00000524681.1
	CYP2C8	ENST00000854631.1		c.856-4904G>A		intron	N/A	ENSP00000524690.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 45210 AN: 148500 Hom.: 7619 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.305 AC: 45265 AN: 148616 Hom.: 7639 Cov.: 32 AF XY: 0.305 AC XY: 22155 AN XY: 72556

African (AFR) AF: 0.466 AC: 18840 AN: 40432

American (AMR) AF: 0.233 AC: 3479 AN: 14910

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1125 AN: 3452

East Asian (EAS) AF: 0.392 AC: 2012 AN: 5132

South Asian (SAS) AF: 0.371 AC: 1746 AN: 4704

European-Finnish (FIN) AF: 0.212 AC: 2156 AN: 10164

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.224 AC: 14914 AN: 66624

Other (OTH) AF: 0.327 AC: 656 AN: 2008

Alfa AF: 0.273 Hom.: 1523

Bravo AF: 0.304

Asia WGS AF: 0.386 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.25
PhyloP100		0.19
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: rs1341162; hg19: chr10-96810612;