10-95048734-T-C

Variant names:

• chr10-95048734-T-C
• rs947173
• NM_000770.3:c.820-2783A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000770.3(CYP2C8):​c.820-2783A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,932 control chromosomes in the GnomAD database, including 11,231 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11231 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.820-2783A>G		intron_variant	Intron 5 of 8	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.610-2783A>G		intron_variant	Intron 5 of 8		NP_001185782.1
CYP2C8	NM_001198855.1	c.610-2783A>G		intron_variant	Intron 6 of 9		NP_001185784.1
CYP2C8	NM_001198854.1	c.514-2783A>G		intron_variant	Intron 4 of 7		NP_001185783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.820-2783A>G		intron_variant	Intron 5 of 8	1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57368 AN: 151814 Hom.: 11215 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.411

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.378 AC: 57419 AN: 151932 Hom.: 11231 Cov.: 32 AF XY: 0.378 AC XY: 28047 AN XY: 74252

African (AFR) AF: 0.476 AC: 19720 AN: 41408

American (AMR) AF: 0.322 AC: 4914 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1440 AN: 3470

East Asian (EAS) AF: 0.390 AC: 2006 AN: 5148

South Asian (SAS) AF: 0.399 AC: 1922 AN: 4818

European-Finnish (FIN) AF: 0.318 AC: 3351 AN: 10552

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22670 AN: 67952

Other (OTH) AF: 0.415 AC: 875 AN: 2110

Alfa AF: 0.280 Hom.: 1261

Bravo AF: 0.382

Asia WGS AF: 0.400 AC: 1393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.68
PhyloP100		0.31
Mutation Taster		=100/0	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: rs947173; hg19: chr10-96808491;