Genetic Variant LOC105378575:n.859C>G (chr10-133526101-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The XR_007062396.1(LOC105378575):n.859C>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 0.0475 in 152,254 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

Frequency

Genomes: 𝑓 0.047 ( 293 hom., cov: 33)

Consequence

LOC105378575
XR_007062396.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.70

Publications

172 publications found

Variant links:

Genes affected

LOC105378575 (HGNC:):

LOC105378575 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=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105378575	XR_007062396.1 link	n.859C>G		non_coding_transcript_exon_variant	Exon 1 of 5
LOC105378575	XR_946512.3 link	n.243C>G		non_coding_transcript_exon_variant	Exon 2 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
CYP2E1	ENST00000463117.6 link	c.-117-695G>C	intron_variant	Intron 1 of 10	5	ENSP00000440689.1
CYP2E1	ENST00000541261.1 link	c.-118+460G>C	intron_variant	Intron 1 of 3	4	ENSP00000437799.1
ENSG00000278518	ENST00000822676.1 link	n.230+659C>G	intron_variant	Intron 1 of 2
ENSG00000278518	ENST00000622716.2 link	n.*152C>G	downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0474

AC:

7214

AN:

152136

Hom.:

286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0574

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0910

Gnomad ASJ

AF:

0.0519

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.0219

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0265

Gnomad OTH

AF:

0.0411

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

GnomAD4 genome

AF:

0.0475

AC:

7226

AN:

152254

Hom.:

293

Cov.:

AF XY:

0.0491

AC XY:

3659

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0572

AC:

2374

AN:

41516

American (AMR)

AF:

0.0917

AC:

1403

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0519

AC:

180

AN:

3470

East Asian (EAS)

AF:

0.204

AC:

1054

AN:

5178

South Asian (SAS)

AF:

0.0129

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0219

AC:

233

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0265

AC:

1805

AN:

68034

Other (OTH)

AF:

0.0412

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

316

632

949

1265

1581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.00975

Hom.:

Bravo

AF:

0.0565

Asia WGS

AF:

0.0750

AC:

261

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.45

(source)

DANN

Benign

0.70

PhyloP100

-2.7

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