rs2860840

Variant names:

• chr10-94735475-C-T
• rs2860840
• NM_000772.3:c.*31C>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.*31C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,608,778 control chromosomes in the GnomAD database, including 99,437 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 0.28 (7353 hom., cov: 33)
  • Exomes 𝑓: 0.35 (92084 hom.)
• Consequence: CYP2C18 NM_000772.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 40 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C18	NM_000772.3	c.*31C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2	c.*31C>T		3_prime_UTR_variant	Exon 8 of 8		NP_001122397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C18	ENST00000285979.11	c.*31C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_000772.3	ENSP00000285979.6
CYP2C18	ENST00000339022.6	c.*31C>T		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000341293.5
ENSG00000276490	ENST00000464755.1	n.931+2037C>T		intron_variant	Intron 6 of 13	2		ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42180 AN: 152020 Hom.: 7342 Cov.: 33

Gnomad AFR AF: 0.0667

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.285

GnomAD2 exomes AF: 0.338 AC: 84502 AN: 249938 AF XY: 0.333

Gnomad AFR exome AF: 0.0623

Gnomad AMR exome AF: 0.521

Gnomad ASJ exome AF: 0.309

Gnomad EAS exome AF: 0.187

Gnomad FIN exome AF: 0.447

Gnomad NFE exome AF: 0.357

Gnomad OTH exome AF: 0.325

GnomAD4 exome AF: 0.347 AC: 505120 AN: 1456640 Hom.: 92084 Cov.: 31 AF XY: 0.343 AC XY: 248518 AN XY: 724468

African (AFR) AF: 0.0537 AC: 1788 AN: 33312

American (AMR) AF: 0.511 AC: 22784 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 8136 AN: 26028

East Asian (EAS) AF: 0.201 AC: 7972 AN: 39610

South Asian (SAS) AF: 0.240 AC: 20669 AN: 86086

European-Finnish (FIN) AF: 0.443 AC: 23653 AN: 53354

Middle Eastern (MID) AF: 0.246 AC: 1412 AN: 5746

European-Non Finnish (NFE) AF: 0.361 AC: 399748 AN: 1107758

Other (OTH) AF: 0.315 AC: 18958 AN: 60178

GnomAD4 genome AF: 0.277 AC: 42199 AN: 152138 Hom.: 7353 Cov.: 33 AF XY: 0.282 AC XY: 20952 AN XY: 74364

African (AFR) AF: 0.0665 AC: 2763 AN: 41554

American (AMR) AF: 0.428 AC: 6543 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1111 AN: 3466

East Asian (EAS) AF: 0.185 AC: 953 AN: 5160

South Asian (SAS) AF: 0.227 AC: 1096 AN: 4826

European-Finnish (FIN) AF: 0.449 AC: 4760 AN: 10592

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23954 AN: 67952

Other (OTH) AF: 0.284 AC: 599 AN: 2110

Alfa AF: 0.313 Hom.: 13892

Bravo AF: 0.269

Asia WGS AF: 0.185 AC: 641 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.59
PhyloP100		-0.26
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: rs2860840; hg19: chr10-96495232; COSMIC: COSV53670641;