10-95050795-T-C

Variant names:

• chr10-95050795-T-C
• rs1341163
• NM_000770.3:c.820-4844A>G

Variant summary

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

The NM_000770.3(CYP2C8):​c.820-4844A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 151,960 control chromosomes in the GnomAD database, including 31,852 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 0.64 (31852 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 2 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.820-4844A>G		intron_variant	Intron 5 of 8	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.610-4844A>G		intron_variant	Intron 5 of 8		NP_001185782.1
CYP2C8	NM_001198855.1	c.610-4844A>G		intron_variant	Intron 6 of 9		NP_001185784.1
CYP2C8	NM_001198854.1	c.514-4844A>G		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.820-4844A>G		intron_variant	Intron 5 of 8	1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97203 AN: 151842 Hom.: 31811 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.640 AC: 97289 AN: 151960 Hom.: 31852 Cov.: 32 AF XY: 0.634 AC XY: 47098 AN XY: 74258

African (AFR) AF: 0.758 AC: 31421 AN: 41450

American (AMR) AF: 0.502 AC: 7658 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2250 AN: 3472

East Asian (EAS) AF: 0.430 AC: 2214 AN: 5148

South Asian (SAS) AF: 0.616 AC: 2973 AN: 4824

European-Finnish (FIN) AF: 0.581 AC: 6128 AN: 10542

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42388 AN: 67952

Other (OTH) AF: 0.653 AC: 1369 AN: 2098

Alfa AF: 0.628 Hom.: 43546

Bravo AF: 0.637

Asia WGS AF: 0.561 AC: 1950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.38
PhyloP100		-1.0
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: rs1341163; hg19: chr10-96810552;