dbSNP rs3813865: LOC105378575:n.604C>G (chr10-133525740-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_946512.3(LOC105378575):n.604C>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 0.0723 in 152,332 control chromosomes in the GnomAD database, including 697 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 0.072 ( 697 hom., cov: 33)

Exomes 𝑓: 0.017 ( 0 hom. )

Consequence

LOC105378575
XR_946512.3 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0140

Publications

14 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:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105378575	XR_946512.3 link	n.604C>G		non_coding_transcript_exon_variant	Exon 2 of 5
LOC105378575	XR_007062396.1 link	n.943+277C>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
CYP2E1	ENST00000463117.6 link	c.-117-1056G>C	intron_variant	Intron 1 of 10	5	ENSP00000440689.1	P05181
CYP2E1	ENST00000541261.1 link	c.-118+99G>C	intron_variant	Intron 1 of 3	4	ENSP00000437799.1	F5H694
ENSG00000278518	ENST00000822676.1 link	n.230+1020C>G	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0725

AC:

11020

AN:

152036

Hom.:

699

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0796

Gnomad ASJ

AF:

0.0518

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.0179

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0214

Gnomad OTH

AF:

0.0747

GnomAD4 exome

AF:

0.0169

AC:

AN:

178

Hom.:

AF XY:

0.0231

AC XY:

AN XY:

130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00676

AC:

AN:

148

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0724

AC:

11013

AN:

152154

Hom.:

697

Cov.:

AF XY:

0.0756

AC XY:

5628

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.131

AC:

5438

AN:

41482

American (AMR)

AF:

0.0794

AC:

1215

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0518

AC:

180

AN:

3472

East Asian (EAS)

AF:

0.226

AC:

1162

AN:

5150

South Asian (SAS)

AF:

0.240

AC:

1154

AN:

4818

European-Finnish (FIN)

AF:

0.0179

AC:

190

AN:

10604

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0214

AC:

1457

AN:

68018

Other (OTH)

AF:

0.0730

AC:

154

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

466

932

1399

1865

2331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0415

Hom.:

Bravo

AF:

0.0765

Asia WGS

AF:

0.230

AC:

802

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

7.1

(source)

DANN

Benign

0.67

PhyloP100

-0.014

PromoterAI

0.023

Neutral

(source)

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