rs7909236

Variant names:

• chr10-95069673-G-T
• rs7909236
• NM_000770.3:c.-271C>A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000770.3(CYP2C8):​c.-271C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,112 control chromosomes in the GnomAD database, including 3,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency: Genomes: 𝑓 0.18 (3221 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-95069673-G-T is Benign according to our data. Variant chr10-95069673-G-T is described in Lovd as [Likely_benign]. Variant chr10-95069673-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.-271C>A		upstream_gene_variant		ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.-519C>A		upstream_gene_variant			NP_001185782.1
CYP2C8	NM_001198855.1	c.-581C>A		upstream_gene_variant			NP_001185784.1
CYP2C8	NM_001198854.1	c.-452C>A		upstream_gene_variant			NP_001185783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.-271C>A		upstream_gene_variant		1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27700 AN: 151994 Hom.: 3216 Cov.: 32

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0852

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.182 AC: 27704 AN: 152112 Hom.: 3221 Cov.: 32 AF XY: 0.185 AC XY: 13772 AN XY: 74354

Gnomad4 AFR AF: 0.0446

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0850

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.163

Alfa AF: 0.221 Hom.: 7995

Bravo AF: 0.170

Asia WGS AF: 0.118 AC: 411 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7909236; hg19: chr10-96829430;