NM_000770.3:c.482-166A>G

Variant names:

• chr10-95065126-T-C
• rs3752988
• NM_000770.3:c.482-166A>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.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
• Publications: 6 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=-0.87).
• 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 rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.482-166A>G		intron_variant	Intron 3 of 8	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.272-166A>G		intron_variant	Intron 3 of 8		NP_001185782.1
CYP2C8	NM_001198855.1	c.272-166A>G		intron_variant	Intron 4 of 9		NP_001185784.1
CYP2C8	NM_001198854.1	c.176-166A>G		intron_variant	Intron 2 of 7		NP_001185783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.482-166A>G		intron_variant	Intron 3 of 8	1	NM_000770.3	ENSP00000360317.3

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

African (AFR) AF: 0.476 AC: 19741 AN: 41468

American (AMR) AF: 0.321 AC: 4902 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1438 AN: 3468

East Asian (EAS) AF: 0.394 AC: 2042 AN: 5178

South Asian (SAS) AF: 0.400 AC: 1928 AN: 4822

European-Finnish (FIN) AF: 0.318 AC: 3356 AN: 10562

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22668 AN: 67980

Other (OTH) AF: 0.416 AC: 880 AN: 2114

Alfa AF: 0.362 Hom.: 19371

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

Jul 05, 2022

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: association

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.69
DANN	Benign	0.72
PhyloP100		-2.2
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: rs3752988; hg19: chr10-96824883;