Genetic Variant ENSG00000278518:n.941T>A (chr10-133527063-A-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000622716.2(ENSG00000278518):n.941T>A 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 0.72 in 304,230 control chromosomes in the GnomAD database, including 83,504 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 0.67 ( 38112 hom., cov: 33)

Exomes 𝑓: 0.77 ( 45392 hom. )

Consequence

ENSG00000278518
ENST00000622716.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.137

Publications

68 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105378575	XR_007062396.1 link	n.-104T>A		upstream_gene_variant
LOC105378575	XR_946512.3 link	n.-104T>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ENSG00000278518	ENST00000622716.2 link	n.941T>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
CYP2E1	ENST00000463117.6 link	c.-40+190A>T	intron_variant	Intron 2 of 10	5	ENSP00000440689.1	P05181
CYP2E1	ENST00000541261.1 link	c.-40+190A>T	intron_variant	Intron 2 of 3	4	ENSP00000437799.1	F5H694
ENSG00000278518	ENST00000822676.1 link	n.-74T>A	upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.673

AC:

102273

AN:

151858

Hom.:

38095

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.865

Gnomad AMR

AF:

0.703

Gnomad ASJ

AF:

0.749

Gnomad EAS

AF:

0.576

Gnomad SAS

AF:

0.647

Gnomad FIN

AF:

0.898

Gnomad MID

AF:

0.718

Gnomad NFE

AF:

0.849

Gnomad OTH

AF:

0.691

GnomAD4 exome

AF:

0.768

AC:

116879

AN:

152254

Hom.:

45392

Cov.:

AF XY:

0.769

AC XY:

58802

AN XY:

76452

show subpopulations

African (AFR)

AF:

0.314

AC:

2047

AN:

6526

American (AMR)

AF:

0.685

AC:

3850

AN:

5622

Ashkenazi Jewish (ASJ)

AF:

0.742

AC:

3421

AN:

4608

East Asian (EAS)

AF:

0.546

AC:

5368

AN:

9834

South Asian (SAS)

AF:

0.637

AC:

3420

AN:

5372

European-Finnish (FIN)

AF:

0.865

AC:

6144

AN:

7104

Middle Eastern (MID)

AF:

0.704

AC:

483

AN:

686

European-Non Finnish (NFE)

AF:

0.826

AC:

85511

AN:

103482

Other (OTH)

AF:

0.736

AC:

6635

AN:

9020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

1146

2292

3438

4584

5730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1026

2052

3078

4104

5130

<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:

0.673

AC:

102311

AN:

151976

Hom.:

38112

Cov.:

AF XY:

0.674

AC XY:

50066

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.318

AC:

13147

AN:

41354

American (AMR)

AF:

0.703

AC:

10738

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.749

AC:

2599

AN:

3470

East Asian (EAS)

AF:

0.577

AC:

2983

AN:

5172

South Asian (SAS)

AF:

0.648

AC:

3124

AN:

4820

European-Finnish (FIN)

AF:

0.898

AC:

9531

AN:

10610

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.849

AC:

57720

AN:

67962

Other (OTH)

AF:

0.695

AC:

1467

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1210

2419

3629

4838

6048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<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:

0.737

Hom.:

4831

Asia WGS

AF:

0.626

AC:

2173

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.0

(source)

DANN

Benign

0.77

PhyloP100

-0.14

PromoterAI

0.00020

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.32

Position offset: -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