rs9629977

Variant names:

• chr10-133545654-C-T
• rs9629977
• ENST00000368520.1:n.1358+7762C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The ENST00000368520.1(CYP2E1):​n.1358+7762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 151,980 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.012 (0 hom., cov: 33)
• Consequence: CYP2E1 ENST00000368520.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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 Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1894/151980) while in subpopulation AFR AF= 0.0437 (1806/41362). AF 95% confidence interval is 0.042. There are 0 homozygotes in gnomad4. There are 903 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000368520.1	n.1358+7762C>T		intron_variant	Intron 5 of 5	1

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1895 AN: 151862 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00374

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.0105

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

GnomAD4 genome AF: 0.0125 AC: 1894 AN: 151980 Hom.: 0 Cov.: 33 AF XY: 0.0122 AC XY: 903 AN XY: 74290

Gnomad4 AFR AF: 0.0437

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00290 Hom.: 1

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9629977; hg19: chr10-135359158;