rs7909236

Variant names:

• chr10-95069673-G-T
• rs7909236
• NM_000770.3:c.-271C>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.-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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 33 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 (AMR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000770.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	NM_000770.3	MANE Select	c.-271C>A		upstream_gene	N/A	NP_000761.3	P10632-1
	CYP2C8	NM_001198853.1		c.-519C>A		upstream_gene	N/A	NP_001185782.1	P10632
	CYP2C8	NM_001198855.1		c.-581C>A		upstream_gene	N/A	NP_001185784.1	P10632

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	ENST00000371270.6	TSL:1 MANE Select	c.-271C>A		upstream_gene	N/A	ENSP00000360317.3	P10632-1
	CYP2C8	ENST00000854622.1		c.-271C>A		upstream_gene	N/A	ENSP00000524681.1
	CYP2C8	ENST00000854631.1		c.-271C>A		upstream_gene	N/A	ENSP00000524690.1

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

African (AFR) AF: 0.0446 AC: 1854 AN: 41536

American (AMR) AF: 0.254 AC: 3882 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 678 AN: 3468

East Asian (EAS) AF: 0.0850 AC: 441 AN: 5186

South Asian (SAS) AF: 0.190 AC: 916 AN: 4818

European-Finnish (FIN) AF: 0.293 AC: 3095 AN: 10566

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16257 AN: 67956

Other (OTH) AF: 0.163 AC: 343 AN: 2106

Alfa AF: 0.212 Hom.: 12296

Bravo AF: 0.170

Asia WGS AF: 0.118 AC: 411 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.39
PhyloP100		-2.5
PromoterAI		0.023	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7909236; hg19: chr10-96829430;