rs6413421

Positions:

• chr10-133532307-T-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.648+23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 1,605,964 control chromosomes in the GnomAD database, including 2,316 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 0.037 (146 hom., cov: 33)
  • Exomes 𝑓: 0.050 (2170 hom.)
• Consequence: CYP2E1 NM_000773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107

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=-0.88).
• BP6: Variant 10-133532307-T-C is Benign according to our data. Variant chr10-133532307-T-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2E1	NM_000773.4	c.648+23T>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.648+23T>C		intron_variant		1	NM_000773.4	ENSP00000252945	P1

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5696 AN: 152150 Hom.: 146 Cov.: 33

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0482

GnomAD3 exomes AF: 0.0422 AC: 10548 AN: 250134 Hom.: 295 AF XY: 0.0453 AC XY: 6130 AN XY: 135200

Gnomad AFR exome AF: 0.0140

Gnomad AMR exome AF: 0.0245

Gnomad ASJ exome AF: 0.0770

Gnomad EAS exome AF: 0.00207

Gnomad SAS exome AF: 0.0592

Gnomad FIN exome AF: 0.0266

Gnomad NFE exome AF: 0.0532

Gnomad OTH exome AF: 0.0477

GnomAD4 exome AF: 0.0501 AC: 72895 AN: 1453696 Hom.: 2170 Cov.: 30 AF XY: 0.0506 AC XY: 36524 AN XY: 722106

Gnomad4 AFR exome AF: 0.0137

Gnomad4 AMR exome AF: 0.0258

Gnomad4 ASJ exome AF: 0.0746

Gnomad4 EAS exome AF: 0.00109

Gnomad4 SAS exome AF: 0.0602

Gnomad4 FIN exome AF: 0.0291

Gnomad4 NFE exome AF: 0.0534

Gnomad4 OTH exome AF: 0.0508

GnomAD4 genome AF: 0.0375 AC: 5704 AN: 152268 Hom.: 146 Cov.: 33 AF XY: 0.0372 AC XY: 2769 AN XY: 74458

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.0348

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.00366

Gnomad4 SAS AF: 0.0640

Gnomad4 FIN AF: 0.0252

Gnomad4 NFE AF: 0.0527

Gnomad4 OTH AF: 0.0477

Alfa AF: 0.0530 Hom.: 263

Bravo AF: 0.0361

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.47

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: rs6413421; hg19: chr10-135345811;