rs11572102

Variant names:

• chr10-95058424-T-A
• rs11572102
• NM_000770.3:c.730A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-95058424-T-A
• chr10-95058424-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000770.3(CYP2C8):​c.730A>T​(p.Ile244Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I244V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CYP2C8 NM_000770.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.26

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12275869).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.730A>T	p.Ile244Phe	missense_variant	Exon 5 of 9	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.520A>T	p.Ile174Phe	missense_variant	Exon 5 of 9		NP_001185782.1
CYP2C8	NM_001198855.1	c.520A>T	p.Ile174Phe	missense_variant	Exon 6 of 10		NP_001185784.1
CYP2C8	NM_001198854.1	c.424A>T	p.Ile142Phe	missense_variant	Exon 4 of 8		NP_001185783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.730A>T	p.Ile244Phe	missense_variant	Exon 5 of 9	1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250870 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135576

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461204 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726888

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.083
DANN	Benign	0.81
DEOGEN2	Benign	0.25	.;.;.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.60	.;T;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.1	.;.;.;L;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.3	.;N;.;N;.
REVEL	Benign	0.27
Sift	Benign	0.066	.;T;.;T;.
Sift4G	Uncertain	0.053	T;T;T;T;D
Polyphen		0.22	.;.;.;B;.
Vest4		0.15
MutPred		0.46		.;.;.;Gain of ubiquitination at K247 (P = 0.1079);.;
MVP		0.47
MPC		0.028
ClinPred		0.059	T
GERP RS		-0.15
Varity_R		0.26
gMVP		0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs11572102; hg19: chr10-96818181;