NM_000772.3:c.643-463G>T

Variant names:

• chr10-94706321-G-T
• rs1409655
• NM_000772.3:c.643-463G>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.643-463G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,990 control chromosomes in the GnomAD database, including 7,421 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 (7421 hom., cov: 31)
• Consequence: CYP2C18 NM_000772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 7 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.422 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C18	NM_000772.3	MANE Select	c.643-463G>T		intron	N/A	NP_000763.1	P33260-1
	CYP2C18	NM_001128925.2		c.642+11244G>T		intron	N/A	NP_001122397.1	P33260-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C18	ENST00000285979.11	TSL:1 MANE Select	c.643-463G>T		intron	N/A	ENSP00000285979.6	P33260-1
	CYP2C18	ENST00000339022.6	TSL:1	c.642+11244G>T		intron	N/A	ENSP00000341293.5	P33260-2
	ENSG00000276490	ENST00000464755.1	TSL:2	n.283-463G>T		intron	N/A	ENSP00000483243.1	A0A087X0B3

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43013 AN: 151874 Hom.: 7410 Cov.: 31

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.283 AC: 43037 AN: 151990 Hom.: 7421 Cov.: 31 AF XY: 0.287 AC XY: 21341 AN XY: 74286

African (AFR) AF: 0.0862 AC: 3574 AN: 41474

American (AMR) AF: 0.430 AC: 6567 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1109 AN: 3468

East Asian (EAS) AF: 0.186 AC: 961 AN: 5164

South Asian (SAS) AF: 0.228 AC: 1098 AN: 4818

European-Finnish (FIN) AF: 0.448 AC: 4725 AN: 10554

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.353 AC: 23980 AN: 67948

Other (OTH) AF: 0.288 AC: 607 AN: 2106

Alfa AF: 0.335 Hom.: 13245

Bravo AF: 0.276

Asia WGS AF: 0.185 AC: 643 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.14
DANN	Benign	0.73
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: rs1409655; hg19: chr10-96466078;