Genetic Variant CYP2C18:c.643-603G>C (chr10-94706181-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000772.3(CYP2C18):c.643-603G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.977 in 152,274 control chromosomes in the GnomAD database, including 72,769 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 0.98 ( 72769 hom., cov: 31)

Consequence

CYP2C18
NM_000772.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.42

Publications

1 publications found

Variant links:

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]

CYP2C18 links:

ENSG00000276490 (HGNC:):

ENSG00000276490 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C18	NM_000772.3 link	c.643-603G>C		intron_variant	Intron 4 of 8	ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2 link	c.642+11104G>C		intron_variant	Intron 4 of 7		NP_001122397.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CYP2C18	ENST00000285979.11 link	c.643-603G>C	intron_variant	Intron 4 of 8	1	NM_000772.3	ENSP00000285979.6
CYP2C18	ENST00000339022.6 link	c.642+11104G>C	intron_variant	Intron 4 of 7	1		ENSP00000341293.5
ENSG00000276490	ENST00000464755.1 link	n.283-603G>C	intron_variant	Intron 2 of 13	2		ENSP00000483243.1

Frequencies

GnomAD3 genomes

AF:

0.977

AC:

148675

AN:

152156

Hom.:

72735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.922

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.993

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.986

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

GnomAD4 genome

AF:

0.977

AC:

148764

AN:

152274

Hom.:

72769

Cov.:

AF XY:

0.978

AC XY:

72836

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.921

AC:

38264

AN:

41538

American (AMR)

AF:

0.993

AC:

15178

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

0.987

AC:

5103

AN:

5170

South Asian (SAS)

AF:

0.999

AC:

4819

AN:

4822

European-Finnish (FIN)

AF:

1.00

AC:

10618

AN:

10618

Middle Eastern (MID)

AF:

0.986

AC:

290

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68021

AN:

68042

Other (OTH)

AF:

0.986

AC:

2087

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

162

325

487

650

812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.997

Hom.:

3322

Bravo

AF:

0.974

Asia WGS

AF:

0.990

AC:

3444

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

2.5

(source)

DANN

Benign

0.31

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over