rs2860840

Positions:

• chr10-94735475-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.*31C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,608,778 control chromosomes in the GnomAD database, including 99,437 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 0.28 (7353 hom., cov: 33)
  • Exomes 𝑓: 0.35 (92084 hom.)
• Consequence: CYP2C18 NM_000772.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C18	NM_000772.3	c.*31C>T		3_prime_UTR_variant	9/9	ENST00000285979.11
CYP2C18	NM_001128925.2	c.*31C>T		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C18	ENST00000285979.11	c.*31C>T		3_prime_UTR_variant	9/9	1	NM_000772.3	P1
CYP2C18	ENST00000339022.6	c.*31C>T		3_prime_UTR_variant	8/8	1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42180 AN: 152020 Hom.: 7342 Cov.: 33

Gnomad AFR AF: 0.0667

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.285

GnomAD3 exomes AF: 0.338 AC: 84502 AN: 249938 Hom.: 16291 AF XY: 0.333 AC XY: 44958 AN XY: 135048

Gnomad AFR exome AF: 0.0623

Gnomad AMR exome AF: 0.521

Gnomad ASJ exome AF: 0.309

Gnomad EAS exome AF: 0.187

Gnomad SAS exome AF: 0.235

Gnomad FIN exome AF: 0.447

Gnomad NFE exome AF: 0.357

Gnomad OTH exome AF: 0.325

GnomAD4 exome AF: 0.347 AC: 505120 AN: 1456640 Hom.: 92084 Cov.: 31 AF XY: 0.343 AC XY: 248518 AN XY: 724468

Gnomad4 AFR exome AF: 0.0537

Gnomad4 AMR exome AF: 0.511

Gnomad4 ASJ exome AF: 0.313

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.443

Gnomad4 NFE exome AF: 0.361

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.277 AC: 42199 AN: 152138 Hom.: 7353 Cov.: 33 AF XY: 0.282 AC XY: 20952 AN XY: 74364

Gnomad4 AFR AF: 0.0665

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.284

Alfa AF: 0.331 Hom.: 9250

Bravo AF: 0.269

Asia WGS AF: 0.185 AC: 641 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.59

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: rs2860840; hg19: chr10-96495232; COSMIC: COSV53670641;