rs2070672

Positions:

• chr10-133527044-A-G

Variant summary

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

The ENST00000622716.1(ENSG00000278518):​n.470T>C 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 0.0548 in 312,078 control chromosomes in the GnomAD database, including 1,050 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 0.071 (695 hom., cov: 33)
  • Exomes 𝑓: 0.039 (355 hom.)
• Consequence: ENST00000622716.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.88).
• BP6: Variant 10-133527044-A-G is Benign according to our data. Variant chr10-133527044-A-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000622716.1	n.470T>C		non_coding_transcript_exon_variant	1/1
CYP2E1	ENST00000463117.6	c.-40+171A>G		intron_variant		5		ENSP00000440689	P1
CYP2E1	ENST00000541261.1	c.-40+171A>G		intron_variant		4		ENSP00000437799

Frequencies

GnomAD3 genomes AF: 0.0713 AC: 10849 AN: 152060 Hom.: 692 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0518

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0206

Gnomad OTH AF: 0.0722

GnomAD4 exome AF: 0.0390 AC: 6240 AN: 159900 Hom.: 355 Cov.: 5 AF XY: 0.0402 AC XY: 3187 AN XY: 79206

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.0801

Gnomad4 ASJ exome AF: 0.0441

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.0194

Gnomad4 NFE exome AF: 0.0182

Gnomad4 OTH exome AF: 0.0553

GnomAD4 genome AF: 0.0713 AC: 10854 AN: 152178 Hom.: 695 Cov.: 33 AF XY: 0.0749 AC XY: 5576 AN XY: 74422

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0785

Gnomad4 ASJ AF: 0.0518

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.0180

Gnomad4 NFE AF: 0.0206

Gnomad4 OTH AF: 0.0705

Alfa AF: 0.0354 Hom.: 315

Bravo AF: 0.0748

Asia WGS AF: 0.234 AC: 813 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	1.1
DANN	Benign	0.62

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: rs2070672; hg19: chr10-135340548;