rs1926706

Positions:

• chr10-94688372-A-G

Variant summary

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

The NM_000772.3(CYP2C18):​c.481+98A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,375,254 control chromosomes in the GnomAD database, including 140,740 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 0.49 (18833 hom., cov: 32)
  • Exomes 𝑓: 0.44 (121907 hom.)
• Consequence: CYP2C18 NM_000772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C18	NM_000772.3	c.481+98A>G		intron_variant		ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2	c.481+98A>G		intron_variant			NP_001122397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C18	ENST00000285979.11	c.481+98A>G		intron_variant		1	NM_000772.3	ENSP00000285979.6
CYP2C18	ENST00000339022.6	c.481+98A>G		intron_variant		1		ENSP00000341293.5
ENSG00000276490	ENST00000464755.1	n.121+98A>G		intron_variant		2		ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73660 AN: 151820 Hom.: 18814 Cov.: 32

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.440 AC: 538358 AN: 1223316 Hom.: 121907 AF XY: 0.445 AC XY: 270474 AN XY: 608236

Gnomad4 AFR exome AF: 0.651

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.436

Gnomad4 EAS exome AF: 0.446

Gnomad4 SAS exome AF: 0.608

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.428

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.485 AC: 73724 AN: 151938 Hom.: 18833 Cov.: 32 AF XY: 0.485 AC XY: 36035 AN XY: 74272

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.462

Alfa AF: 0.466 Hom.: 2559

Bravo AF: 0.479

Asia WGS AF: 0.534 AC: 1857 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	0.41
DANN	Benign	0.32

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: rs1926706; hg19: chr10-96448129;