NM_000770.3:c.730A>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000770.3(CYP2C8):​c.730A>G​(p.Ile244Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000591 in 1,613,508 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0028 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (1 hom.)
• Consequence: CYP2C8 NM_000770.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.26
• Publications: 12 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0046361685).
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	NM_000770.3	MANE Select	c.730A>G	p.Ile244Val	missense	Exon 5 of 9	NP_000761.3
	CYP2C8	NM_001198853.1		c.520A>G	p.Ile174Val	missense	Exon 5 of 9	NP_001185782.1
	CYP2C8	NM_001198855.1		c.520A>G	p.Ile174Val	missense	Exon 6 of 10	NP_001185784.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	ENST00000371270.6	TSL:1 MANE Select	c.730A>G	p.Ile244Val	missense	Exon 5 of 9	ENSP00000360317.3
	CYP2C8	ENST00000623108.3	TSL:2	c.520A>G	p.Ile174Val	missense	Exon 5 of 9	ENSP00000485110.1
	CYP2C8	ENST00000535898.5	TSL:2	c.424A>G	p.Ile142Val	missense	Exon 4 of 8	ENSP00000445062.1

Frequencies

GnomAD3 genomes AF: 0.00283 AC: 431 AN: 152186 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00994

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000670 AC: 168 AN: 250870 AF XY: 0.000472

Gnomad AFR exome AF: 0.00941

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000357 AC: 522 AN: 1461204 Hom.: 1 Cov.: 31 AF XY: 0.000310 AC XY: 225 AN XY: 726888

African (AFR) AF: 0.0114 AC: 380 AN: 33444

American (AMR) AF: 0.000314 AC: 14 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5758

European-Non Finnish (NFE) AF: 0.0000783 AC: 87 AN: 1111668

Other (OTH) AF: 0.000613 AC: 37 AN: 60368

GnomAD4 genome AF: 0.00283 AC: 431 AN: 152304 Hom.: 2 Cov.: 32 AF XY: 0.00281 AC XY: 209 AN XY: 74474

African (AFR) AF: 0.00991 AC: 412 AN: 41572

American (AMR) AF: 0.000850 AC: 13 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000983 Hom.: 1

Bravo AF: 0.00337

ESP6500AA AF: 0.0102 AC: 45

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000824 AC: 100

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.010
DANN	Benign	0.29
DEOGEN2	Benign	0.053	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.31	N
PhyloP100		-4.3
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.091
Sift	Benign	0.43	T
Sift4G	Benign	0.47	T
Polyphen		0.0020	B
Vest4		0.036
MVP		0.31
MPC		0.021
ClinPred		0.0035	T
GERP RS		-0.15
Varity_R		0.057
gMVP		0.13
Mutation Taster		=91/9	polymorphism

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: rs11572102; hg19: chr10-96818181;