10-94704973-G-A

Variant names:

• chr10-94704973-G-A
• rs7896133
• NM_000772.3:c.643-1811G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000772.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C18	NM_000772.3	MANE Select	c.643-1811G>A		intron	N/A	NP_000763.1
	CYP2C18	NM_001128925.2		c.642+9896G>A		intron	N/A	NP_001122397.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C18	ENST00000285979.11	TSL:1 MANE Select	c.643-1811G>A		intron	N/A	ENSP00000285979.6
	CYP2C18	ENST00000339022.6	TSL:1	c.642+9896G>A		intron	N/A	ENSP00000341293.5
	ENSG00000276490	ENST00000464755.1	TSL:2	n.283-1811G>A		intron	N/A	ENSP00000483243.1

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

African (AFR) AF: 0.111 AC: 4609 AN: 41494

American (AMR) AF: 0.0562 AC: 859 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 293 AN: 3472

East Asian (EAS) AF: 0.0990 AC: 510 AN: 5152

South Asian (SAS) AF: 0.121 AC: 580 AN: 4808

European-Finnish (FIN) AF: 0.0512 AC: 542 AN: 10590

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0666 AC: 4532 AN: 68004

Other (OTH) AF: 0.0800 AC: 169 AN: 2112

Alfa AF: 0.0728 Hom.: 739

Bravo AF: 0.0796

Asia WGS AF: 0.136 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.4
DANN	Benign	0.34
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7896133; hg19: chr10-96464730;