Genetic Variant CYP2C18:c.*283G>T (chr10-94735727-G-T) – 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.*283G>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 0.178 in 351,756 control chromosomes in the GnomAD database, including 6,139 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 0.18 ( 2610 hom., cov: 32)

Exomes 𝑓: 0.18 ( 3529 hom. )

Consequence

CYP2C18
NM_000772.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.250

Publications

18 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:

Genome browser will be placed here

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 (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C18	NM_000772.3 link	c.*283G>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2 link	c.*283G>T		3_prime_UTR_variant	Exon 8 of 8		NP_001122397.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CYP2C18	ENST00000285979.11 link	c.*283G>T	3_prime_UTR_variant	Exon 9 of 9	1	NM_000772.3	ENSP00000285979.6
ENSG00000276490	ENST00000464755.1 link	n.931+2289G>T	intron_variant	Intron 6 of 13	2		ENSP00000483243.1
CYP2C18	ENST00000339022.6 link	c.*283G>T	downstream_gene_variant		1		ENSP00000341293.5

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26749

AN:

151878

Hom.:

2605

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.156

GnomAD4 exome

AF:

0.180

AC:

35888

AN:

199760

Hom.:

3529

Cov.:

AF XY:

0.182

AC XY:

18460

AN XY:

101316

show subpopulations

African (AFR)

AF:

0.220

AC:

1603

AN:

7272

American (AMR)

AF:

0.127

AC:

1017

AN:

7988

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

1026

AN:

7186

East Asian (EAS)

AF:

0.319

AC:

5628

AN:

17626

South Asian (SAS)

AF:

0.355

AC:

2485

AN:

6998

European-Finnish (FIN)

AF:

0.186

AC:

2332

AN:

12544

Middle Eastern (MID)

AF:

0.122

AC:

117

AN:

956

European-Non Finnish (NFE)

AF:

0.154

AC:

19414

AN:

125978

Other (OTH)

AF:

0.172

AC:

2266

AN:

13212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1378

2755

4133

5510

6888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

182

364

546

728

910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.176

AC:

26771

AN:

151996

Hom.:

2610

Cov.:

AF XY:

0.180

AC XY:

13375

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.207

AC:

8570

AN:

41462

American (AMR)

AF:

0.134

AC:

2042

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

459

AN:

3468

East Asian (EAS)

AF:

0.311

AC:

1604

AN:

5160

South Asian (SAS)

AF:

0.331

AC:

1594

AN:

4818

European-Finnish (FIN)

AF:

0.183

AC:

1932

AN:

10540

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.148

AC:

10037

AN:

67972

Other (OTH)

AF:

0.160

AC:

339

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1112

2223

3335

4446

5558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<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:

0.154

Hom.:

6013

Bravo

AF:

0.170

Asia WGS

AF:

0.306

AC:

1062

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

3.4

(source)

DANN

Benign

0.26

PhyloP100

0.25

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over