10-95037513-T-C

Variant names:

• chr10-95037513-T-C
• rs11572177
• NM_000770.3:c.1292-204A>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.1292-204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,050 control chromosomes in the GnomAD database, including 7,514 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 0.31 (7514 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.1292-204A>G		intron_variant	Intron 8 of 8	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.1082-204A>G		intron_variant	Intron 8 of 8		NP_001185782.1
CYP2C8	NM_001198855.1	c.1082-204A>G		intron_variant	Intron 9 of 9		NP_001185784.1
CYP2C8	NM_001198854.1	c.986-204A>G		intron_variant	Intron 7 of 7		NP_001185783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.1292-204A>G		intron_variant	Intron 8 of 8	1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47009 AN: 151930 Hom.: 7498 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0669

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.310 AC: 47061 AN: 152050 Hom.: 7514 Cov.: 32 AF XY: 0.303 AC XY: 22558 AN XY: 74348

African (AFR) AF: 0.334 AC: 13853 AN: 41462

American (AMR) AF: 0.236 AC: 3609 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3468

East Asian (EAS) AF: 0.0670 AC: 348 AN: 5192

South Asian (SAS) AF: 0.268 AC: 1291 AN: 4814

European-Finnish (FIN) AF: 0.297 AC: 3143 AN: 10584

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22796 AN: 67938

Other (OTH) AF: 0.291 AC: 612 AN: 2106

Alfa AF: 0.323 Hom.: 30627

Bravo AF: 0.303

Asia WGS AF: 0.202 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.21
DANN	Benign	0.45
PhyloP100		-1.4
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: rs11572177; hg19: chr10-96797270;