chr10-94735727-G-T

Position:

• chr10-94735727-G-T

Variant summary

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

The NM_000772.3(CYP2C18):​c.*283G>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 0.178 in 351,756 control chromosomes in the GnomAD database, including 6,139 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 0.18 (2610 hom., cov: 32)
  • Exomes 𝑓: 0.18 (3529 hom.)
• Consequence: CYP2C18 NM_000772.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250

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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C18	NM_000772.3	c.*283G>T		3_prime_UTR_variant	9/9	ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2	c.*283G>T		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.*283G>T		3_prime_UTR_variant	9/9	1	NM_000772.3	ENSP00000285979.6
ENSG00000276490	ENST00000464755.1	n.931+2289G>T		intron_variant		2		ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26749 AN: 151878 Hom.: 2605 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.180 AC: 35888 AN: 199760 Hom.: 3529 Cov.: 0 AF XY: 0.182 AC XY: 18460 AN XY: 101316

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.355

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.176 AC: 26771 AN: 151996 Hom.: 2610 Cov.: 32 AF XY: 0.180 AC XY: 13375 AN XY: 74256

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.160

Alfa AF: 0.151 Hom.: 3711

Bravo AF: 0.170

Asia WGS AF: 0.306 AC: 1062 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	3.4
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: rs1042194; hg19: chr10-96495484;