rs7896133

Positions:

• chr10-94704973-G-A

Variant summary

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

The NM_000772.3(CYP2C18):​c.643-1811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0798 in 152,110 control chromosomes in the GnomAD database, including 556 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 0.080 (556 hom., cov: 32)
• Consequence: CYP2C18 NM_000772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-1.05).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C18	NM_000772.3	c.643-1811G>A		intron_variant		ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2	c.642+9896G>A		intron_variant			NP_001122397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C18	ENST00000285979.11	c.643-1811G>A		intron_variant		1	NM_000772.3	ENSP00000285979	P1
CYP2C18	ENST00000339022.6	c.642+9896G>A		intron_variant		1		ENSP00000341293

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12114 AN: 151992 Hom.: 551 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.0990

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0512

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.0780

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

GnomAD4 genome AF: 0.0798 AC: 12141 AN: 152110 Hom.: 556 Cov.: 32 AF XY: 0.0800 AC XY: 5950 AN XY: 74358

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0562

Gnomad4 ASJ AF: 0.0844

Gnomad4 EAS AF: 0.0990

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0512

Gnomad4 NFE AF: 0.0666

Gnomad4 OTH AF: 0.0800

Alfa AF: 0.0722 Hom.: 567

Bravo AF: 0.0796

Asia WGS AF: 0.136 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.4
DANN	Benign	0.34

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: rs7896133; hg19: chr10-96464730;