Genetic Variant NM_000772.3:c.819+2182G>A (chr10-94709142-G-A) – 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.819+2182G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,108 control chromosomes in the GnomAD database, including 1,068 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 0.10 ( 1068 hom., cov: 32)

Consequence

CYP2C18
NM_000772.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.375

Publications

19 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=-0.98).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C18	NM_000772.3 link	c.819+2182G>A		intron_variant	Intron 5 of 8	ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2 link	c.643-11254G>A		intron_variant	Intron 4 of 7		NP_001122397.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CYP2C18	ENST00000285979.11 link	c.819+2182G>A	intron_variant	Intron 5 of 8	1	NM_000772.3	ENSP00000285979.6
CYP2C18	ENST00000339022.6 link	c.643-11254G>A	intron_variant	Intron 4 of 7	1		ENSP00000341293.5
ENSG00000276490	ENST00000464755.1 link	n.459+2182G>A	intron_variant	Intron 3 of 13	2		ENSP00000483243.1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15882

AN:

151990

Hom.:

1068

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0273

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.0791

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0932

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.0910

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

GnomAD4 genome

AF:

0.104

AC:

15883

AN:

152108

Hom.:

1068

Cov.:

AF XY:

0.103

AC XY:

7668

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0272

AC:

1130

AN:

41510

American (AMR)

AF:

0.150

AC:

2288

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0791

AC:

274

AN:

3464

East Asian (EAS)

AF:

0.00193

AC:

AN:

5174

South Asian (SAS)

AF:

0.0933

AC:

450

AN:

4822

European-Finnish (FIN)

AF:

0.138

AC:

1462

AN:

10564

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.146

AC:

9907

AN:

67982

Other (OTH)

AF:

0.0900

AC:

190

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

717

1434

2150

2867

3584

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.132

Hom.:

2920

Bravo

AF:

0.101

Asia WGS

AF:

0.0440

AC:

152

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

6.7

(source)

DANN

Benign

0.56

PhyloP100

-0.38

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