rs2515641

Variant names:

• chr10-133537858-C-T
• rs2515641
• NM_000773.4:c.1263C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-133537858-C-T
• chr10-133537858-C-A
• chr10-133537858-C-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP6_Moderate BP7 BA1

The NM_000773.4(CYP2E1):​c.1263C>T​(p.Phe421Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,612,742 control chromosomes in the GnomAD database, including 22,115 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (7973 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14142 hom.)
• Consequence: CYP2E1 NM_000773.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.107
• Publications: 73 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 -11 ACMG points.

• BP6: Variant 10-133537858-C-T is Benign according to our data. Variant chr10-133537858-C-T is described in ClinVar as Benign. ClinVar VariationId is 768403.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.107 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000773.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	NM_000773.4	MANE Select	c.1263C>T	p.Phe421Phe	synonymous	Exon 8 of 9	NP_000764.1	P05181

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2E1	ENST00000252945.8	TSL:1 MANE Select	c.1263C>T	p.Phe421Phe	synonymous	Exon 8 of 9	ENSP00000252945.3	P05181
	CYP2E1	ENST00000421586.5	TSL:1	c.1002C>T	p.Phe334Phe	synonymous	Exon 7 of 8	ENSP00000412754.1	H0Y7H4
	CYP2E1	ENST00000418356.1	TSL:1	c.852C>T	p.Phe284Phe	synonymous	Exon 6 of 7	ENSP00000397299.1	H0Y593

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39082 AN: 151696 Hom.: 7950 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.0717

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0766

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.127 AC: 185075 AN: 1460928 Hom.: 14142 Cov.: 32 AF XY: 0.126 AC XY: 91630 AN XY: 726738

African (AFR) AF: 0.609 AC: 20374 AN: 33436

American (AMR) AF: 0.174 AC: 7759 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 4469 AN: 26114

East Asian (EAS) AF: 0.170 AC: 6740 AN: 39686

South Asian (SAS) AF: 0.155 AC: 13344 AN: 86194

European-Finnish (FIN) AF: 0.0838 AC: 4472 AN: 53388

Middle Eastern (MID) AF: 0.229 AC: 1318 AN: 5768

European-Non Finnish (NFE) AF: 0.105 AC: 116971 AN: 1111350

Other (OTH) AF: 0.160 AC: 9628 AN: 60346

GnomAD4 genome AF: 0.258 AC: 39144 AN: 151814 Hom.: 7973 Cov.: 32 AF XY: 0.254 AC XY: 18852 AN XY: 74244

African (AFR) AF: 0.600 AC: 24791 AN: 41320

American (AMR) AF: 0.197 AC: 2999 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 602 AN: 3466

East Asian (EAS) AF: 0.179 AC: 924 AN: 5162

South Asian (SAS) AF: 0.168 AC: 808 AN: 4806

European-Finnish (FIN) AF: 0.0766 AC: 812 AN: 10598

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7555 AN: 67896

Other (OTH) AF: 0.245 AC: 517 AN: 2112

Alfa AF: 0.161 Hom.: 12711

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	13
PhyloP100		0.11

Splicing

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

Other links and lift over

dbSNP: rs2515641; hg19: chr10-135351362;