rs11572082

Variant names:

• chr10-95067165-C-G
• rs11572082
• NM_000770.3:c.481+43G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-95067165-C-G
• chr10-95067165-C-T

Variant summary

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

The ENST00000371270.6(CYP2C8):​c.481+43G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,612,770 control chromosomes in the GnomAD database, including 9,713 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 0.080 (610 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9103 hom.)
• Consequence: CYP2C8 ENST00000371270.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.888
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371270.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	NM_000770.3	MANE Select	c.481+43G>C		intron	N/A	NP_000761.3
	CYP2C8	NM_001198853.1		c.271+43G>C		intron	N/A	NP_001185782.1
	CYP2C8	NM_001198855.1		c.271+43G>C		intron	N/A	NP_001185784.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	ENST00000371270.6	TSL:1 MANE Select	c.481+43G>C		intron	N/A	ENSP00000360317.3
	CYP2C8	ENST00000623108.3	TSL:2	c.271+43G>C		intron	N/A	ENSP00000485110.1
	CYP2C8	ENST00000535898.5	TSL:2	c.175+43G>C		intron	N/A	ENSP00000445062.1

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12140 AN: 152070 Hom.: 610 Cov.: 32

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.0925

Gnomad ASJ AF: 0.0912

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0380

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.0833 AC: 20888 AN: 250850 AF XY: 0.0848

Gnomad AFR exome AF: 0.0202

Gnomad AMR exome AF: 0.0675

Gnomad ASJ exome AF: 0.0990

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.106 AC: 154184 AN: 1460582 Hom.: 9103 Cov.: 32 AF XY: 0.104 AC XY: 75643 AN XY: 726666

African (AFR) AF: 0.0185 AC: 620 AN: 33464

American (AMR) AF: 0.0716 AC: 3202 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 2498 AN: 26124

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39690

South Asian (SAS) AF: 0.0431 AC: 3721 AN: 86238

European-Finnish (FIN) AF: 0.110 AC: 5858 AN: 53396

Middle Eastern (MID) AF: 0.120 AC: 691 AN: 5750

European-Non Finnish (NFE) AF: 0.119 AC: 131792 AN: 1110900

Other (OTH) AF: 0.0961 AC: 5795 AN: 60324

GnomAD4 genome AF: 0.0797 AC: 12136 AN: 152188 Hom.: 610 Cov.: 32 AF XY: 0.0791 AC XY: 5885 AN XY: 74394

African (AFR) AF: 0.0211 AC: 878 AN: 41552

American (AMR) AF: 0.0923 AC: 1410 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0912 AC: 316 AN: 3466

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5162

South Asian (SAS) AF: 0.0380 AC: 183 AN: 4818

European-Finnish (FIN) AF: 0.114 AC: 1202 AN: 10588

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7742 AN: 68014

Other (OTH) AF: 0.104 AC: 218 AN: 2106

Alfa AF: 0.0509 Hom.: 65

Bravo AF: 0.0777

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.80
DANN	Benign	0.43
PhyloP100		-0.89
PromoterAI		0.11	Neutral
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: rs11572082; hg19: chr10-96826922;