rs11572080

Variant names:

• chr10-95067273-C-T
• rs11572080
• NM_000770.3:c.416G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-95067273-C-T
• chr10-95067273-C-A
• chr10-95067273-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000770.3(CYP2C8):​c.416G>A​(p.Arg139Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,614,040 control chromosomes in the GnomAD database, including 9,726 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.080 (613 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9113 hom.)
• Consequence: CYP2C8 NM_000770.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.144
• Publications: 203 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019239187).
• BP6: Variant 10-95067273-C-T is Benign according to our data. Variant chr10-95067273-C-T is described in ClinVar as Benign. ClinVar VariationId is 545635.Status of the report is no_assertion_criteria_provided, 0 stars.
• 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: 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.416G>A	p.Arg139Lys	missense	Exon 3 of 9	NP_000761.3	P10632-1
	CYP2C8	NM_001198853.1		c.206G>A	p.Arg69Lys	missense	Exon 3 of 9	NP_001185782.1	P10632
	CYP2C8	NM_001198855.1		c.206G>A	p.Arg69Lys	missense	Exon 4 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.416G>A	p.Arg139Lys	missense	Exon 3 of 9	ENSP00000360317.3	P10632-1
	CYP2C8	ENST00000854622.1		c.416G>A	p.Arg139Lys	missense	Exon 3 of 10	ENSP00000524681.1
	CYP2C8	ENST00000854631.1		c.416G>A	p.Arg139Lys	missense	Exon 3 of 10	ENSP00000524690.1

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12146 AN: 152124 Hom.: 613 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0923

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.0834 AC: 20965 AN: 251460 AF XY: 0.0849

Gnomad AFR exome AF: 0.0202

Gnomad AMR exome AF: 0.0674

Gnomad ASJ exome AF: 0.0989

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: 154652 AN: 1461798 Hom.: 9113 Cov.: 33 AF XY: 0.104 AC XY: 75850 AN XY: 727204

African (AFR) AF: 0.0186 AC: 622 AN: 33480

American (AMR) AF: 0.0717 AC: 3208 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 2499 AN: 26134

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39700

South Asian (SAS) AF: 0.0432 AC: 3727 AN: 86258

European-Finnish (FIN) AF: 0.110 AC: 5863 AN: 53418

Middle Eastern (MID) AF: 0.121 AC: 695 AN: 5764

European-Non Finnish (NFE) AF: 0.119 AC: 132209 AN: 1111928

Other (OTH) AF: 0.0964 AC: 5822 AN: 60396

GnomAD4 genome AF: 0.0798 AC: 12142 AN: 152242 Hom.: 613 Cov.: 32 AF XY: 0.0792 AC XY: 5892 AN XY: 74430

African (AFR) AF: 0.0211 AC: 877 AN: 41562

American (AMR) AF: 0.0922 AC: 1409 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 317 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0380 AC: 183 AN: 4822

European-Finnish (FIN) AF: 0.114 AC: 1205 AN: 10596

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

European-Non Finnish (NFE) AF: 0.114 AC: 7747 AN: 68006

Other (OTH) AF: 0.103 AC: 217 AN: 2110

Alfa AF: 0.0828 Hom.: 473

Bravo AF: 0.0777

TwinsUK AF: 0.123 AC: 456

ALSPAC AF: 0.119 AC: 458

ESP6500AA AF: 0.0245 AC: 108

ESP6500EA AF: 0.117 AC: 1002

ExAC AF: 0.0825 AC: 10023

Asia WGS AF: 0.0150 AC: 54 AN: 3478

EpiCase AF: 0.120

EpiControl AF: 0.119

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CYP2C8-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.14
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.039
Sift	Benign	0.19	T
Sift4G	Benign	0.42	T
Polyphen		0.015	B
Vest4		0.057
MPC		0.036
ClinPred		0.013	T
GERP RS		2.8
PromoterAI		0.030	Neutral
Varity_R		0.23
gMVP		0.068
Mutation Taster		=84/16	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: rs11572080; hg19: chr10-96827030; COSMIC: COSV64875934;