rs2296684

Variant names:

• chr10-94706513-C-A
• rs2296684
• NM_000772.3:c.643-271C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-94706513-C-A
• chr10-94706513-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000772.3(CYP2C18):​c.643-271C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 152,052 control chromosomes in the GnomAD database, including 148 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 0.025 (148 hom., cov: 32)
• Consequence: CYP2C18 NM_000772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C18	NM_000772.3	c.643-271C>A		intron_variant	Intron 4 of 8	ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2	c.642+11436C>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.643-271C>A		intron_variant	Intron 4 of 8	1	NM_000772.3	ENSP00000285979.6
CYP2C18	ENST00000339022.6	c.642+11436C>A		intron_variant	Intron 4 of 7	1		ENSP00000341293.5
ENSG00000276490	ENST00000464755.1	n.283-271C>A		intron_variant	Intron 2 of 13	2		ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3829 AN: 151934 Hom.: 143 Cov.: 32

Gnomad AFR AF: 0.0751

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00793

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0616

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.000379

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00315

Gnomad OTH AF: 0.0173

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

GnomAD4 genome AF: 0.0253 AC: 3843 AN: 152052 Hom.: 148 Cov.: 32 AF XY: 0.0250 AC XY: 1857 AN XY: 74342

African (AFR) AF: 0.0751 AC: 3114 AN: 41480

American (AMR) AF: 0.00792 AC: 121 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.0615 AC: 318 AN: 5170

South Asian (SAS) AF: 0.00581 AC: 28 AN: 4820

European-Finnish (FIN) AF: 0.000379 AC: 4 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00315 AC: 214 AN: 67966

Other (OTH) AF: 0.0209 AC: 44 AN: 2108

Alfa AF: 0.0107 Hom.: 61

Bravo AF: 0.0274

Asia WGS AF: 0.0510 AC: 178 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	0.71
DANN	Benign	0.23
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism

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: rs2296684; hg19: chr10-96466270;