rs2296680

Variant names:

• chr10-94707181-G-A
• rs2296680
• NM_000772.3:c.819+221G>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.819+221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,014 control chromosomes in the GnomAD database, including 2,475 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 0.17 (2475 hom., cov: 32)
• Consequence: CYP2C18 NM_000772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.768
• Publications: 6 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=-0.93).
• 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 rank	MANE	Protein	UniProt
CYP2C18	NM_000772.3	c.819+221G>A		intron_variant	Intron 5 of 8	ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2	c.642+12104G>A		intron_variant	Intron 4 of 7		NP_001122397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C18	ENST00000285979.11	c.819+221G>A		intron_variant	Intron 5 of 8	1	NM_000772.3	ENSP00000285979.6
CYP2C18	ENST00000339022.6	c.642+12104G>A		intron_variant	Intron 4 of 7	1		ENSP00000341293.5
ENSG00000276490	ENST00000464755.1	n.459+221G>A		intron_variant	Intron 3 of 13	2		ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26073 AN: 151896 Hom.: 2470 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.172 AC: 26093 AN: 152014 Hom.: 2475 Cov.: 32 AF XY: 0.176 AC XY: 13039 AN XY: 74280

African (AFR) AF: 0.192 AC: 7957 AN: 41454

American (AMR) AF: 0.131 AC: 2003 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 456 AN: 3466

East Asian (EAS) AF: 0.312 AC: 1615 AN: 5174

South Asian (SAS) AF: 0.331 AC: 1589 AN: 4804

European-Finnish (FIN) AF: 0.182 AC: 1925 AN: 10554

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10025 AN: 67982

Other (OTH) AF: 0.156 AC: 330 AN: 2112

Alfa AF: 0.151 Hom.: 2378

Bravo AF: 0.165

Asia WGS AF: 0.305 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.65
DANN	Benign	0.43
PhyloP100		-0.77
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: rs2296680; hg19: chr10-96466938; COSMIC: COSV53672608;