NM_000770.3:c.169-712A>G

Variant names:

• chr10-95068403-T-C
• rs1934956
• NM_000770.3:c.169-712A>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.169-712A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,140 control chromosomes in the GnomAD database, including 51,591 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 0.82 (51591 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 9 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.169-712A>G		intron_variant	Intron 1 of 8	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.-42-712A>G		intron_variant	Intron 1 of 8		NP_001185782.1
CYP2C8	NM_001198855.1	c.-43+164A>G		intron_variant	Intron 2 of 9		NP_001185784.1
CYP2C8	NM_001198854.1	c.25+794A>G		intron_variant	Intron 1 of 7		NP_001185783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.169-712A>G		intron_variant	Intron 1 of 8	1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124672 AN: 152022 Hom.: 51547 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.816

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

GnomAD4 genome AF: 0.820 AC: 124765 AN: 152140 Hom.: 51591 Cov.: 32 AF XY: 0.818 AC XY: 60820 AN XY: 74376

African (AFR) AF: 0.789 AC: 32738 AN: 41494

American (AMR) AF: 0.756 AC: 11552 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2927 AN: 3470

East Asian (EAS) AF: 0.537 AC: 2769 AN: 5156

South Asian (SAS) AF: 0.808 AC: 3905 AN: 4830

European-Finnish (FIN) AF: 0.879 AC: 9309 AN: 10594

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.863 AC: 58713 AN: 68000

Other (OTH) AF: 0.816 AC: 1726 AN: 2114

Alfa AF: 0.841 Hom.: 179402

Bravo AF: 0.804

Asia WGS AF: 0.687 AC: 2389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.8
DANN	Benign	0.58
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1934956; hg19: chr10-96828160;