rs3813865

Positions:

• chr10-133525740-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

Genes affected

LOC105378575 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LOC105378575	XR_946512.3	n.604C>G		non_coding_transcript_exon_variant	2/5
LOC105378575	XR_007062396.1	n.943+277C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000463117.6	c.-117-1056G>C		intron_variant		5		ENSP00000440689	P1
CYP2E1	ENST00000541261.1	c.-118+99G>C		intron_variant		4		ENSP00000437799

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 11020 AN: 152036 Hom.: 699 Cov.: 33

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: 3 AN: 178 Hom.: 0 AF XY: 0.0231 AC XY: 3 AN XY: 130

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00676

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0724 AC: 11013 AN: 152154 Hom.: 697 Cov.: 33 AF XY: 0.0756 AC XY: 5628 AN XY: 74400

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0794

Gnomad4 ASJ AF: 0.0518

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.0179

Gnomad4 NFE AF: 0.0214

Gnomad4 OTH AF: 0.0730

Alfa AF: 0.0415 Hom.: 28

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
DANN	Benign	0.67

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

LitVar

Other links and lift over

dbSNP: rs3813865; hg19: chr10-135339244;