Genetic Variant ENSG00000278518:n.1415A>G (chr10-133526589-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.1415A>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 0.126 in 152,656 control chromosomes in the GnomAD database, including 1,882 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 0.13 ( 1880 hom., cov: 33)

Exomes 𝑓: 0.17 ( 2 hom. )

Consequence

ENSG00000278518
ENST00000622716.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.280

Publications

7 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=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105378575	XR_007062396.1 link	n.371A>G		non_coding_transcript_exon_variant	Exon 1 of 5
LOC105378575	XR_946512.3 link	n.200+171A>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
ENSG00000278518	ENST00000622716.2 link	n.1415A>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
CYP2E1	ENST00000463117.6 link	c.-117-207T>C	intron_variant	Intron 1 of 10	5	ENSP00000440689.1
CYP2E1	ENST00000541261.1 link	c.-117-207T>C	intron_variant	Intron 1 of 3	4	ENSP00000437799.1
ENSG00000278518	ENST00000822676.1 link	n.230+171A>G	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19115

AN:

151894

Hom.:

1866

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.0485

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.0842

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.0281

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.0498

Gnomad OTH

AF:

0.106

GnomAD4 exome

AF:

0.174

AC:

112

AN:

644

Hom.:

Cov.:

AF XY:

0.169

AC XY:

AN XY:

314

show subpopulations

African (AFR)

AF:

0.278

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.171

AC:

101

AN:

592

Other (OTH)

AF:

0.227

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.126

AC:

19164

AN:

152012

Hom.:

1880

Cov.:

AF XY:

0.125

AC XY:

9287

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.284

AC:

11738

AN:

41386

American (AMR)

AF:

0.132

AC:

2023

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0842

AC:

292

AN:

3466

East Asian (EAS)

AF:

0.204

AC:

1059

AN:

5182

South Asian (SAS)

AF:

0.0176

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0281

AC:

298

AN:

10610

Middle Eastern (MID)

AF:

0.0582

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0498

AC:

3385

AN:

67958

Other (OTH)

AF:

0.106

AC:

223

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

663

1325

1988

2650

3313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<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:

0.125

Hom.:

223

Asia WGS

AF:

0.0880

AC:

309

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

2.1

(source)

DANN

Benign

0.29

PhyloP100

-0.28

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