NM_000770.3:c.1292-434G>A

Variant names:

• chr10-95037743-C-T
• rs1934952
• NM_000770.3:c.1292-434G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000770.3(CYP2C8):​c.1292-434G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,048 control chromosomes in the GnomAD database, including 7,437 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 (7437 hom., cov: 33)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35
• Publications: 5 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=-0.91).
• 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.1292-434G>A		intron_variant	Intron 8 of 8	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.1082-434G>A		intron_variant	Intron 8 of 8		NP_001185782.1
CYP2C8	NM_001198855.1	c.1082-434G>A		intron_variant	Intron 9 of 9		NP_001185784.1
CYP2C8	NM_001198854.1	c.986-434G>A		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.1292-434G>A		intron_variant	Intron 8 of 8	1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46790 AN: 151930 Hom.: 7425 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0669

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.308 AC: 46834 AN: 152048 Hom.: 7437 Cov.: 33 AF XY: 0.302 AC XY: 22468 AN XY: 74306

African (AFR) AF: 0.330 AC: 13663 AN: 41462

American (AMR) AF: 0.235 AC: 3592 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3472

East Asian (EAS) AF: 0.0671 AC: 348 AN: 5188

South Asian (SAS) AF: 0.268 AC: 1292 AN: 4812

European-Finnish (FIN) AF: 0.298 AC: 3137 AN: 10544

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

European-Non Finnish (NFE) AF: 0.335 AC: 22783 AN: 67972

Other (OTH) AF: 0.289 AC: 610 AN: 2112

Alfa AF: 0.321 Hom.: 9768

Bravo AF: 0.302

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.3
DANN	Benign	0.37
PhyloP100		2.4
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: rs1934952; hg19: chr10-96797500;