chr10-95067209-C-T

Variant names:

• chr10-95067209-C-T
• rs11572081
• NM_000770.3:c.480G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_000770.3(CYP2C8):​c.480G>A​(p.Lys160Lys) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00866 in 1,613,980 control chromosomes in the GnomAD database, including 1,023 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.045 (569 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (454 hom.)
• Consequence: CYP2C8 NM_000770.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.0005856
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -8.39
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 10-95067209-C-T is Benign according to our data. Variant chr10-95067209-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056915.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-8.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 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.480G>A	p.Lys160Lys	splice_region synonymous	Exon 3 of 9	NP_000761.3
	CYP2C8	NM_001198853.1		c.270G>A	p.Lys90Lys	splice_region synonymous	Exon 3 of 9	NP_001185782.1
	CYP2C8	NM_001198855.1		c.270G>A	p.Lys90Lys	splice_region synonymous	Exon 4 of 10	NP_001185784.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	ENST00000371270.6	TSL:1 MANE Select	c.480G>A	p.Lys160Lys	splice_region synonymous	Exon 3 of 9	ENSP00000360317.3
	CYP2C8	ENST00000854622.1		c.480G>A	p.Lys160Lys	splice_region synonymous	Exon 3 of 10	ENSP00000524681.1
	CYP2C8	ENST00000854631.1		c.480G>A	p.Lys160Lys	splice_region synonymous	Exon 3 of 10	ENSP00000524690.1

Frequencies

GnomAD3 genomes AF: 0.0446 AC: 6784 AN: 152084 Hom.: 567 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.0307

GnomAD2 exomes AF: 0.0119 AC: 2993 AN: 251402 AF XY: 0.00881

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.00821

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000721

Gnomad OTH exome AF: 0.00929

GnomAD4 exome AF: 0.00492 AC: 7192 AN: 1461778 Hom.: 454 Cov.: 33 AF XY: 0.00426 AC XY: 3099 AN XY: 727192

African (AFR) AF: 0.162 AC: 5406 AN: 33470

American (AMR) AF: 0.00950 AC: 425 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00989 AC: 57 AN: 5762

European-Non Finnish (NFE) AF: 0.000561 AC: 624 AN: 1111938

Other (OTH) AF: 0.0108 AC: 654 AN: 60386

GnomAD4 genome AF: 0.0446 AC: 6791 AN: 152202 Hom.: 569 Cov.: 32 AF XY: 0.0427 AC XY: 3178 AN XY: 74432

African (AFR) AF: 0.154 AC: 6371 AN: 41494

American (AMR) AF: 0.0195 AC: 298 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000765 AC: 52 AN: 68014

Other (OTH) AF: 0.0304 AC: 64 AN: 2108

Alfa AF: 0.0169 Hom.: 434

Bravo AF: 0.0512

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.000948

ClinVar

ClinVar submissions as Germline

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
BayesDel_noAF	Benign	-0.35
CADD	Benign	0.49
DANN	Benign	0.84
PhyloP100		-8.4
PromoterAI		0.10	Neutral
Mutation Taster		=37/63	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00059
dbscSNV1_RF	Benign	0.13
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: rs11572081; hg19: chr10-96826966;