Genetic Variant ENSG00000278518:n.1635A>G (chr10-133526369-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000622716.2(ENSG00000278518):n.1635A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.045 in 152,230 control chromosomes in the GnomAD database, including 275 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 0.045 ( 275 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

ENSG00000278518
ENST00000622716.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.00

Publications

9 publications found

Variant links:

Genes affected

ENSG00000278518 (HGNC:):

ENSG00000278518 links:

CYP2E1 (HGNC:2631): (cytochrome P450 family 2 subfamily E member 1) 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 and is induced by ethanol, the diabetic state, and starvation. The enzyme metabolizes both endogenous substrates, such as ethanol, acetone, and acetal, as well as exogenous substrates including benzene, carbon tetrachloride, ethylene glycol, and nitrosamines which are premutagens found in cigarette smoke. Due to its many substrates, this enzyme may be involved in such varied processes as gluconeogenesis, hepatic cirrhosis, diabetes, and cancer. [provided by RefSeq, Jul 2008]

CYP2E1 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105378575	XR_007062396.1 link	n.591A>G		non_coding_transcript_exon_variant	Exon 1 of 5
LOC105378575	XR_946512.3 link	n.201-226A>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ENSG00000278518	ENST00000622716.2 link	n.1635A>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
CYP2E1	ENST00000463117.6 link	c.-117-427T>C	intron_variant	Intron 1 of 10	5	ENSP00000440689.1	P05181
CYP2E1	ENST00000541261.1 link	c.-117-427T>C	intron_variant	Intron 1 of 3	4	ENSP00000437799.1	F5H694
ENSG00000278518	ENST00000822676.1 link	n.230+391A>G	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0450

AC:

6838

AN:

152112

Hom.:

269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0488

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0902

Gnomad ASJ

AF:

0.0519

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.0132

Gnomad FIN

AF:

0.0218

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0264

Gnomad OTH

AF:

0.0392

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0450

AC:

6848

AN:

152230

Hom.:

275

Cov.:

AF XY:

0.0467

AC XY:

3479

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0486

AC:

2019

AN:

41510

American (AMR)

AF:

0.0909

AC:

1390

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0519

AC:

180

AN:

3468

East Asian (EAS)

AF:

0.204

AC:

1056

AN:

5180

South Asian (SAS)

AF:

0.0128

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0218

AC:

231

AN:

10614

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0264

AC:

1799

AN:

68020

Other (OTH)

AF:

0.0393

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

309

617

926

1234

1543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0124

Hom.:

Bravo

AF:

0.0538

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.8

(source)

DANN

Benign

0.72

PhyloP100

2.0

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