rs148348784

Variant names:

• chr10-95038912-T-C
• rs148348784
• NM_000770.3:c.1276A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000770.3(CYP2C8):​c.1276A>G​(p.Met426Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,613,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: CYP2C8 NM_000770.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18628046).

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.1276A>G	p.Met426Val	missense	Exon 8 of 9	NP_000761.3	P10632-1
	CYP2C8	NM_001198853.1		c.1066A>G	p.Met356Val	missense	Exon 8 of 9	NP_001185782.1	P10632
	CYP2C8	NM_001198855.1		c.1066A>G	p.Met356Val	missense	Exon 9 of 10	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.1276A>G	p.Met426Val	missense	Exon 8 of 9	ENSP00000360317.3	P10632-1
	CYP2C8	ENST00000854622.1		c.1357A>G	p.Met453Val	missense	Exon 9 of 10	ENSP00000524681.1
	CYP2C8	ENST00000854631.1		c.1312A>G	p.Met438Val	missense	Exon 9 of 10	ENSP00000524690.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000127 AC: 32 AN: 251404 AF XY: 0.000125

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000146 AC: 213 AN: 1461628 Hom.: 0 Cov.: 30 AF XY: 0.000151 AC XY: 110 AN XY: 727126

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.000358 AC: 16 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000169 AC: 188 AN: 1111784

Other (OTH) AF: 0.000116 AC: 7 AN: 60392

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74362

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000185 Hom.: 0

Bravo AF: 0.000113

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.77
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.18
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.11
Sift	Benign	0.32	T
Sift4G	Benign	0.35	T
Polyphen		0.20	B
Vest4		0.22
MVP		0.47
MPC		0.025
ClinPred		0.057	T
GERP RS		0.38
Varity_R		0.52
gMVP		0.10
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs148348784; hg19: chr10-96798669;