NM_000770.3:c.820-5337C>G

Variant names:

• chr10-95051288-G-C
• rs1113129
• NM_000770.3:c.820-5337C>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.820-5337C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,896 control chromosomes in the GnomAD database, including 7,646 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 (7646 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 12 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 = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.820-5337C>G		intron_variant	Intron 5 of 8	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.610-5337C>G		intron_variant	Intron 5 of 8		NP_001185782.1
CYP2C8	NM_001198855.1	c.610-5337C>G		intron_variant	Intron 6 of 9		NP_001185784.1
CYP2C8	NM_001198854.1	c.514-5337C>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.820-5337C>G		intron_variant	Intron 5 of 8	1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45236 AN: 151778 Hom.: 7626 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.298 AC: 45291 AN: 151896 Hom.: 7646 Cov.: 32 AF XY: 0.299 AC XY: 22158 AN XY: 74208

African (AFR) AF: 0.455 AC: 18869 AN: 41476

American (AMR) AF: 0.228 AC: 3476 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1123 AN: 3470

East Asian (EAS) AF: 0.393 AC: 2029 AN: 5162

South Asian (SAS) AF: 0.362 AC: 1740 AN: 4810

European-Finnish (FIN) AF: 0.204 AC: 2144 AN: 10494

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14915 AN: 67934

Other (OTH) AF: 0.312 AC: 660 AN: 2114

Alfa AF: 0.109 Hom.: 160

Bravo AF: 0.304

Asia WGS AF: 0.386 AC: 1337 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.18
PhyloP100		0.21
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: rs1113129; hg19: chr10-96811045;