dbSNP rs149450201: CYP2C18:p.Ser209Arg (chr10-94695062-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000772.3(CYP2C18):c.627C>A(p.Ser209Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,459,944 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S209S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CYP2C18
NM_000772.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.138

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C18	NM_000772.3 link	c.627C>A	p.Ser209Arg	missense_variant	Exon 4 of 9	ENST00000285979.11	NP_000763.1	P33260-1Q7Z348
CYP2C18	NM_001128925.2 link	c.627C>A	p.Ser209Arg	missense_variant	Exon 4 of 8		NP_001122397.1	P33260-2Q7Z348

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP2C18	ENST00000285979.11 link	c.627C>A	p.Ser209Arg	missense_variant	Exon 4 of 9	1	NM_000772.3	ENSP00000285979.6	P33260-1
CYP2C18	ENST00000339022.6 link	c.627C>A	p.Ser209Arg	missense_variant	Exon 4 of 8	1		ENSP00000341293.5	P33260-2
ENSG00000276490	ENST00000464755.1 link	n.267C>A		non_coding_transcript_exon_variant	Exon 2 of 14	2		ENSP00000483243.1	A0A087X0B3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000800

AC:

AN:

249944

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1459944

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726278

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.0000448

AC:

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39574

South Asian (SAS)

AF:

0.00

AC:

AN:

86048

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4990

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111508

Other (OTH)

AF:

0.00

AC:

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.44

T;T

M_CAP

Benign

0.064

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Benign

-0.49

MutationAssessor

Pathogenic

3.1

M;M

PhyloP100

-0.14

PROVEAN

Uncertain

-3.7

D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.047

D;D

Polyphen

0.87

P;.

Vest4

0.35

MutPred

0.81

Gain of solvent accessibility (P = 0.0171);Gain of solvent accessibility (P = 0.0171);

MVP

0.75

MPC

0.028

ClinPred

0.95

GERP RS

1.1

Varity_R

0.77

gMVP

0.29

Mutation Taster

=100/0

polymorphism

(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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rs149450201

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