10-94709875-C-T

Position:

• chr10-94709875-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000772.3(CYP2C18):​c.819+2915C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,094 control chromosomes in the GnomAD database, including 4,174 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 0.23 (4174 hom., cov: 33)
• Consequence: CYP2C18 NM_000772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

Genes affected

CYP2C18 (HGNC:2620): (cytochrome P450 family 2 subfamily C member 18) 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 but its specific substrate has not yet been determined. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. An additional gene, CYP2C17, was once thought to exist; however, CYP2C17 is now considered an artefact based on a chimera of CYP2C18 and CYP2C19. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000276490 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C18	NM_000772.3	c.819+2915C>T		intron_variant		ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2	c.643-10521C>T		intron_variant			NP_001122397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C18	ENST00000285979.11	c.819+2915C>T		intron_variant		1	NM_000772.3	ENSP00000285979.6
CYP2C18	ENST00000339022.6	c.643-10521C>T		intron_variant		1		ENSP00000341293.5
ENSG00000276490	ENST00000464755.1	n.459+2915C>T		intron_variant		2		ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34252 AN: 151974 Hom.: 4166 Cov.: 33

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.225 AC: 34268 AN: 152094 Hom.: 4174 Cov.: 33 AF XY: 0.222 AC XY: 16467 AN XY: 74324

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.0712

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.219

Alfa AF: 0.191 Hom.: 1416

Bravo AF: 0.223

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs7917985; hg19: chr10-96469632;