rs1926706

Variant names:

• chr10-94688372-A-G
• rs1926706
• NM_000772.3:c.481+98A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 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.481+98A>G		intron	N/A	NP_000763.1
	CYP2C18	NM_001128925.2		c.481+98A>G		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.481+98A>G		intron	N/A	ENSP00000285979.6
	CYP2C18	ENST00000339022.6	TSL:1	c.481+98A>G		intron	N/A	ENSP00000341293.5
	ENSG00000276490	ENST00000464755.1	TSL:2	n.121+98A>G		intron	N/A	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

African (AFR) AF: 0.651 AC: 17013 AN: 26152

American (AMR) AF: 0.279 AC: 7182 AN: 25748

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 8963 AN: 20580

East Asian (EAS) AF: 0.446 AC: 15415 AN: 34530

South Asian (SAS) AF: 0.608 AC: 38656 AN: 63542

European-Finnish (FIN) AF: 0.422 AC: 19656 AN: 46550

Middle Eastern (MID) AF: 0.431 AC: 1556 AN: 3612

European-Non Finnish (NFE) AF: 0.428 AC: 406965 AN: 951258

Other (OTH) AF: 0.447 AC: 22952 AN: 51344

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

African (AFR) AF: 0.637 AC: 26398 AN: 41422

American (AMR) AF: 0.336 AC: 5134 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1494 AN: 3468

East Asian (EAS) AF: 0.422 AC: 2182 AN: 5174

South Asian (SAS) AF: 0.617 AC: 2967 AN: 4806

European-Finnish (FIN) AF: 0.420 AC: 4431 AN: 10562

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.436 AC: 29591 AN: 67940

Other (OTH) AF: 0.462 AC: 975 AN: 2110

Alfa AF: 0.468 Hom.: 3174

Bravo AF: 0.479

Asia WGS AF: 0.534 AC: 1857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.32
PhyloP100		0.32
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: rs1926706; hg19: chr10-96448129; COSMIC: COSV107258933;