rs6413420

Positions:

• chr10-133527325-G-T

Variant summary

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

The ENST00000622716.1(ENSG00000278518):​n.189C>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 0.0499 in 1,457,132 control chromosomes in the GnomAD database, including 2,163 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 0.039 (150 hom., cov: 34)
  • Exomes 𝑓: 0.051 (2013 hom.)
• Consequence: ENST00000622716.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-133527325-G-T is Benign according to our data. Variant chr10-133527325-G-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2E1	NM_000773.4			upstream_gene_variant		ENST00000252945.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000622716.1	n.189C>A		non_coding_transcript_exon_variant	1/1
CYP2E1	ENST00000463117.6	c.-39-32G>T		intron_variant		5		P1
CYP2E1	ENST00000541261.1	c.-39-32G>T		intron_variant		4
CYP2E1	ENST00000252945.8			upstream_gene_variant		1	NM_000773.4	P1

Frequencies

GnomAD3 genomes AF: 0.0394 AC: 5907 AN: 149802 Hom.: 150 Cov.: 34

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0353

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0770

Gnomad EAS AF: 0.00342

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.0262

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.0494

GnomAD4 exome AF: 0.0511 AC: 66804 AN: 1307210 Hom.: 2013 Cov.: 19 AF XY: 0.0516 AC XY: 33246 AN XY: 644540

Gnomad4 AFR exome AF: 0.0155

Gnomad4 AMR exome AF: 0.0264

Gnomad4 ASJ exome AF: 0.0752

Gnomad4 EAS exome AF: 0.000702

Gnomad4 SAS exome AF: 0.0664

Gnomad4 FIN exome AF: 0.0304

Gnomad4 NFE exome AF: 0.0540

Gnomad4 OTH exome AF: 0.0523

GnomAD4 genome AF: 0.0395 AC: 5915 AN: 149922 Hom.: 150 Cov.: 34 AF XY: 0.0394 AC XY: 2882 AN XY: 73070

Gnomad4 AFR AF: 0.0174

Gnomad4 AMR AF: 0.0354

Gnomad4 ASJ AF: 0.0770

Gnomad4 EAS AF: 0.00343

Gnomad4 SAS AF: 0.0733

Gnomad4 FIN AF: 0.0262

Gnomad4 NFE AF: 0.0537

Gnomad4 OTH AF: 0.0488

Alfa AF: 0.0537 Hom.: 400

Bravo AF: 0.0373

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.54

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: rs6413420; hg19: chr10-135340829;