rs2031920

chr10-133526341-C-T

Variant summary

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

The ENST00000622716.1(ENSG00000278518):n.1173G>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 0.0334 in 152,114 control chromosomes in the GnomAD database, including 221 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 0.033 (221 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ENST00000622716.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.980

Genes affected

(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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105378575	XR_946512.3	n.201-198G>A		intron_variant, non_coding_transcript_variant
LOC105378575	XR_007062396.1	n.619G>A		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000622716.1	n.1173G>A		non_coding_transcript_exon_variant	1/1
CYP2E1	ENST00000463117.6	c.-117-455C>T		intron_variant		5		P1
CYP2E1	ENST00000541261.1	c.-117-455C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 5070 AN: 151996 Hom.: 215 Cov.: 33

Gnomad AFR AF: 0.00759

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0875

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0350

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0334 AC: 5082 AN: 152114 Hom.: 221 Cov.: 33 AF XY: 0.0356 AC XY: 2648 AN XY: 74368

Gnomad4 AFR AF: 0.00757

Gnomad4 AMR AF: 0.0882

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.0127

Gnomad4 FIN AF: 0.0218

Gnomad4 NFE AF: 0.0263

Gnomad4 OTH AF: 0.0351

Alfa AF: 0.0290 Hom.: 93

Bravo AF: 0.0402

Asia WGS AF: 0.0710 AC: 249 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.22
Dann	Benign	0.30

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: rs2031920; hg19: chr10-135339845;