rs7898759

Variant names:

• chr10-95040597-T-C
• rs7898759
• NM_000770.3:c.1150-1559A>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.1150-1559A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,020 control chromosomes in the GnomAD database, including 36,585 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 0.69 (36585 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.1150-1559A>G		intron_variant	Intron 7 of 8	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.940-1559A>G		intron_variant	Intron 7 of 8		NP_001185782.1
CYP2C8	NM_001198855.1	c.940-1559A>G		intron_variant	Intron 8 of 9		NP_001185784.1
CYP2C8	NM_001198854.1	c.844-1559A>G		intron_variant	Intron 6 of 7		NP_001185783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.1150-1559A>G		intron_variant	Intron 7 of 8	1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104306 AN: 151902 Hom.: 36533 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.687 AC: 104407 AN: 152020 Hom.: 36585 Cov.: 32 AF XY: 0.681 AC XY: 50594 AN XY: 74304

African (AFR) AF: 0.807 AC: 33473 AN: 41482

American (AMR) AF: 0.557 AC: 8517 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2452 AN: 3472

East Asian (EAS) AF: 0.460 AC: 2376 AN: 5162

South Asian (SAS) AF: 0.669 AC: 3219 AN: 4812

European-Finnish (FIN) AF: 0.616 AC: 6491 AN: 10542

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45469 AN: 67952

Other (OTH) AF: 0.705 AC: 1490 AN: 2114

Alfa AF: 0.648 Hom.: 6864

Bravo AF: 0.684

Asia WGS AF: 0.605 AC: 2100 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	3.5
DANN	Benign	0.55
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: rs7898759; hg19: chr10-96800354;