rs6413421

Variant names:

• chr10-133532307-T-C
• rs6413421
• NM_000773.4:c.648+23T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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 rank	MANE	Protein	UniProt
CYP2E1	NM_000773.4	c.648+23T>C		intron_variant	Intron 4 of 8	ENST00000252945.8	NP_000764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2E1	ENST00000252945.8	c.648+23T>C		intron_variant	Intron 4 of 8	1	NM_000773.4	ENSP00000252945.3

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

GnomAD2 exomes AF: 0.0422 AC: 10548 AN: 250134 AF XY: 0.0453

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 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

African (AFR) AF: 0.0137 AC: 457 AN: 33328

American (AMR) AF: 0.0258 AC: 1151 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.0746 AC: 1937 AN: 25978

East Asian (EAS) AF: 0.00109 AC: 43 AN: 39510

South Asian (SAS) AF: 0.0602 AC: 5178 AN: 85950

European-Finnish (FIN) AF: 0.0291 AC: 1548 AN: 53202

Middle Eastern (MID) AF: 0.0883 AC: 507 AN: 5740

European-Non Finnish (NFE) AF: 0.0534 AC: 59022 AN: 1105366

Other (OTH) AF: 0.0508 AC: 3052 AN: 60072

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

African (AFR) AF: 0.0138 AC: 573 AN: 41536

American (AMR) AF: 0.0348 AC: 532 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 260 AN: 3472

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5186

South Asian (SAS) AF: 0.0640 AC: 309 AN: 4830

European-Finnish (FIN) AF: 0.0252 AC: 267 AN: 10612

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0527 AC: 3586 AN: 68012

Other (OTH) AF: 0.0477 AC: 101 AN: 2116

Alfa AF: 0.0490 Hom.: 574

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
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6413421; hg19: chr10-135345811;