10-133537633-G-C

Position:

• chr10-133537633-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000773.4(CYP2E1):​c.1156-118G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 902,148 control chromosomes in the GnomAD database, including 324,270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.74 (44458 hom., cov: 33)
  • Exomes 𝑓: 0.86 (279812 hom.)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

Genes affected

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-133537633-G-C is Benign according to our data. Variant chr10-133537633-G-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2E1	NM_000773.4	c.1156-118G>C		intron_variant		ENST00000252945.8	NP_000764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8	c.1156-118G>C		intron_variant		1	NM_000773.4	ENSP00000252945	P1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111630 AN: 151794 Hom.: 44438 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.747

GnomAD4 exome AF: 0.862 AC: 646615 AN: 750236 Hom.: 279812 Cov.: 10 AF XY: 0.862 AC XY: 331611 AN XY: 384482

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.819

Gnomad4 ASJ exome AF: 0.825

Gnomad4 EAS exome AF: 0.831

Gnomad4 SAS exome AF: 0.845

Gnomad4 FIN exome AF: 0.914

Gnomad4 NFE exome AF: 0.885

Gnomad4 OTH exome AF: 0.831

GnomAD4 genome AF: 0.735 AC: 111685 AN: 151912 Hom.: 44458 Cov.: 33 AF XY: 0.739 AC XY: 54905 AN XY: 74268

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.923

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.750

Alfa AF: 0.713 Hom.: 2147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.65

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: rs2070676; hg19: chr10-135351137;