chr10-95067362-T-TA

Variant names:

• chr10-95067362-T-TA
• rs11572078
• NM_000770.3:c.332-6dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000770.3(CYP2C8):​c.332-6dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,613,462 control chromosomes in the GnomAD database, including 52,419 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (7548 hom., cov: 19)
  • Exomes 𝑓: 0.24 (44871 hom.)
• Consequence: CYP2C8 NM_000770.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.927
• Publications: 15 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.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.446 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	NM_000770.3	MANE Select	c.332-6dupT		splice_region intron	N/A	NP_000761.3
	CYP2C8	NM_001198853.1		c.122-6dupT		splice_region intron	N/A	NP_001185782.1
	CYP2C8	NM_001198855.1		c.122-6dupT		splice_region intron	N/A	NP_001185784.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	ENST00000371270.6	TSL:1 MANE Select	c.332-6dupT		splice_region intron	N/A	ENSP00000360317.3
	CYP2C8	ENST00000628935.1	TSL:5	c.68dupT	p.Leu23PhefsTer34	frameshift	Exon 1 of 6	ENSP00000487145.1
	CYP2C8	ENST00000479946.2	TSL:2	n.630dupT		non_coding_transcript_exon	Exon 2 of 8

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45014 AN: 151624 Hom.: 7529 Cov.: 19

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.307

GnomAD2 exomes AF: 0.261 AC: 65413 AN: 250816 AF XY: 0.264

Gnomad AFR exome AF: 0.454

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.387

Gnomad FIN exome AF: 0.202

Gnomad NFE exome AF: 0.220

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.238 AC: 348286 AN: 1461718 Hom.: 44871 Cov.: 37 AF XY: 0.242 AC XY: 175777 AN XY: 727164

African (AFR) AF: 0.463 AC: 15481 AN: 33470

American (AMR) AF: 0.174 AC: 7774 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 8804 AN: 26134

East Asian (EAS) AF: 0.416 AC: 16516 AN: 39694

South Asian (SAS) AF: 0.356 AC: 30690 AN: 86252

European-Finnish (FIN) AF: 0.201 AC: 10737 AN: 53416

Middle Eastern (MID) AF: 0.317 AC: 1825 AN: 5764

European-Non Finnish (NFE) AF: 0.216 AC: 240420 AN: 1111904

Other (OTH) AF: 0.266 AC: 16039 AN: 60388

GnomAD4 genome AF: 0.297 AC: 45068 AN: 151744 Hom.: 7548 Cov.: 19 AF XY: 0.297 AC XY: 22049 AN XY: 74118

African (AFR) AF: 0.451 AC: 18654 AN: 41366

American (AMR) AF: 0.228 AC: 3485 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1124 AN: 3466

East Asian (EAS) AF: 0.392 AC: 2015 AN: 5144

South Asian (SAS) AF: 0.361 AC: 1734 AN: 4798

European-Finnish (FIN) AF: 0.204 AC: 2136 AN: 10492

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14926 AN: 67920

Other (OTH) AF: 0.311 AC: 656 AN: 2106

Alfa AF: 0.171 Hom.: 469

EpiCase AF: 0.233

EpiControl AF: 0.238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.93
Mutation Taster		=136/64	polymorphism (auto)

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: rs11572078; hg19: chr10-96827119; COSMIC: COSV107469516;