rs3752988

chr10-95065126-T-C

Variant summary

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

The NM_000770.3(CYP2C8):c.482-166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,074 control chromosomes in the GnomAD database, including 11,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.38 (11253 hom., cov: 33)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -2.17

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C8	NM_000770.3	c.482-166A>G		intron_variant		ENST00000371270.6
CYP2C8	NM_001198853.1	c.272-166A>G		intron_variant
CYP2C8	NM_001198854.1	c.176-166A>G		intron_variant
CYP2C8	NM_001198855.1	c.272-166A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C8	ENST00000371270.6	c.482-166A>G		intron_variant		1	NM_000770.3	P1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57425 AN: 151956 Hom.: 11237 Cov.: 33

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.378 AC: 57476 AN: 152074 Hom.: 11253 Cov.: 33 AF XY: 0.378 AC XY: 28104 AN XY: 74374

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.416

Alfa AF: 0.355 Hom.: 11358

Bravo AF: 0.382

Asia WGS AF: 0.400 AC: 1390 AN: 3474

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.69
Dann	Benign	0.72

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: rs3752988; hg19: chr10-96824883;