rs11572177

Positions:

• chr10-95037513-T-C

Variant summary

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

The NM_000770.3(CYP2C8):​c.1292-204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,050 control chromosomes in the GnomAD database, including 7,514 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 0.31 (7514 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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=-0.99).
• BP6: Variant 10-95037513-T-C is Benign according to our data. Variant chr10-95037513-T-C is described in Lovd as [Likely_benign].
• 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/exons	MANE	UniProt
CYP2C8	NM_000770.3	c.1292-204A>G		intron_variant		ENST00000371270.6
CYP2C8	NM_001198853.1	c.1082-204A>G		intron_variant
CYP2C8	NM_001198854.1	c.986-204A>G		intron_variant
CYP2C8	NM_001198855.1	c.1082-204A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C8	ENST00000371270.6	c.1292-204A>G		intron_variant		1	NM_000770.3	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47009 AN: 151930 Hom.: 7498 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0669

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.310 AC: 47061 AN: 152050 Hom.: 7514 Cov.: 32 AF XY: 0.303 AC XY: 22558 AN XY: 74348

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.0670

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.291

Alfa AF: 0.325 Hom.: 13660

Bravo AF: 0.303

Asia WGS AF: 0.202 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.21
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs11572177; hg19: chr10-96797270;