rs1326830

Positions:

• chr10-94736036-C-A
• chr10-94736036-C-T

Variant summary

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

The ENST00000285979.11(CYP2C18):​c.*592C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 152,274 control chromosomes in the GnomAD database, including 248 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 0.025 (248 hom., cov: 32)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: CYP2C18 ENST00000285979.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C18	NM_000772.3	c.*592C>A		3_prime_UTR_variant	9/9	ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2	c.*592C>A		3_prime_UTR_variant	8/8		NP_001122397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C18	ENST00000285979.11	c.*592C>A		3_prime_UTR_variant	9/9	1	NM_000772.3	ENSP00000285979	P1

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3809 AN: 151968 Hom.: 245 Cov.: 32

Gnomad AFR AF: 0.00360

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0751

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00916

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.0106 AC: 2 AN: 188 Hom.: 0 Cov.: 0 AF XY: 0.00893 AC XY: 1 AN XY: 112

Gnomad4 AMR exome AF: 0.0417

Gnomad4 SAS exome AF: 0.250

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0251 AC: 3820 AN: 152086 Hom.: 248 Cov.: 32 AF XY: 0.0321 AC XY: 2386 AN XY: 74332

Gnomad4 AFR AF: 0.00359

Gnomad4 AMR AF: 0.0219

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0751

Gnomad4 NFE AF: 0.00916

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0146 Hom.: 142

Bravo AF: 0.0181

Asia WGS AF: 0.167 AC: 580 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	0.12
DANN	Benign	0.26

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: rs1326830; hg19: chr10-96495793;