10-95037713-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000770.3(CYP2C8):c.1292-404G>A 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 152,040 control chromosomes in the GnomAD database, including 36,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.69 (36575 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -1.88

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• 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/exons	MANE	UniProt
CYP2C8	NM_000770.3	c.1292-404G>A		intron_variant		ENST00000371270.6
CYP2C8	NM_001198853.1	c.1082-404G>A		intron_variant
CYP2C8	NM_001198854.1	c.986-404G>A		intron_variant
CYP2C8	NM_001198855.1	c.1082-404G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C8	ENST00000371270.6	c.1292-404G>A		intron_variant		1	NM_000770.3	P1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104304 AN: 151922 Hom.: 36523 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.738

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: 0.704

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

GnomAD4 genome AF: 0.687 AC: 104405 AN: 152040 Hom.: 36575 Cov.: 32 AF XY: 0.681 AC XY: 50604 AN XY: 74318

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.706

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.706

Alfa AF: 0.668 Hom.: 68685

Bravo AF: 0.684

Asia WGS AF: 0.607 AC: 2109 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to Other:1

association, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 05, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.13
Dann	Benign	0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs1934953; hg19: chr10-96797470;