rs11572076

chr10-95067393-C-T

Variant summary

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

The NM_000770.3(CYP2C8):c.332-36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,614,038 control chromosomes in the GnomAD database, including 916 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 0.044 (466 hom., cov: 33)
  • Exomes 𝑓: 0.0074 (450 hom.)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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 (MetaRNN=0.00172019).
• BP6: Variant 10-95067393-C-T is Benign according to our data. Variant chr10-95067393-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C8	NM_000770.3	c.332-36G>A		intron_variant		ENST00000371270.6
CYP2C8	NM_001198853.1	c.122-36G>A		intron_variant
CYP2C8	NM_001198854.1	c.26-36G>A		intron_variant
CYP2C8	NM_001198855.1	c.122-36G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C8	ENST00000371270.6	c.332-36G>A		intron_variant		1	NM_000770.3	P1

Frequencies

GnomAD3 genomes AF: 0.0440 AC: 6695 AN: 152140 Hom.: 464 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00282

Gnomad OTH AF: 0.0406

GnomAD3 exomes AF: 0.0151 AC: 3777 AN: 250318 Hom.: 177 AF XY: 0.0132 AC XY: 1787 AN XY: 135512

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.00788

Gnomad ASJ exome AF: 0.0141

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.0194

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.00312

Gnomad OTH exome AF: 0.00986

GnomAD4 exome AF: 0.00736 AC: 10763 AN: 1461780 Hom.: 450 Cov.: 37 AF XY: 0.00734 AC XY: 5335 AN XY: 727182

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.00944

Gnomad4 ASJ exome AF: 0.0149

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0203

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.00195

Gnomad4 OTH exome AF: 0.0134

GnomAD4 genome AF: 0.0441 AC: 6708 AN: 152258 Hom.: 466 Cov.: 33 AF XY: 0.0430 AC XY: 3205 AN XY: 74458

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0164

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00282

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0104 Hom.: 113

Bravo AF: 0.0504

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.147 AC: 647

ESP6500EA AF: 0.00360 AC: 31

ExAC AF: 0.0184 AC: 2237

Asia WGS AF: 0.0170 AC: 59 AN: 3478

EpiCase AF: 0.00387

EpiControl AF: 0.00469

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.38
Dann	Benign	0.32
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P
Sift4G	Benign	0.062	T
Vest4		0.015
ClinPred		0.00079	T
GERP RS		-0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs11572076; hg19: chr10-96827150;