rs10857748

Variant names:

• chr10-133558806-T-C
• rs10857748
• ENST00000368520.1:n.5504T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000368520.1(CYP2E1):​n.5504T>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 0.108 in 1,487,782 control chromosomes in the GnomAD database, including 10,061 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 0.098 (888 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9173 hom.)
• Consequence: CYP2E1 ENST00000368520.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• Publications: 9 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]

SYCE1 (HGNC:28852): (synaptonemal complex central element protein 1) This gene encodes a member of the synaptonemal complex, which links homologous chromosomes during prophase I of meiosis. The tripartite structure of the complex is highly conserved amongst metazoans. It consists of two lateral elements and a central region formed by transverse elements and a central element. The protein encoded by this gene localizes to the central element and is required for initiation and elongation of the synapsis. Allelic variants of this gene have been associated with premature ovarian failure and spermatogenic failure. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

SYCE1 Gene-Disease associations (from GenCC):

• premature ovarian failure 12

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• spermatogenic failure 15

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCE1	NM_001143764.3	c.271+71A>G		intron_variant	Intron 4 of 12	ENST00000343131.7	NP_001137236.1
SYCE1	NM_001143763.2	c.271+71A>G		intron_variant	Intron 4 of 12		NP_001137235.1
SYCE1	NM_130784.4	c.163+71A>G		intron_variant	Intron 4 of 12		NP_570140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYCE1	ENST00000343131.7	c.271+71A>G		intron_variant	Intron 4 of 12	1	NM_001143764.3	ENSP00000341282.5

Frequencies

GnomAD3 genomes AF: 0.0978 AC: 14833 AN: 151724 Hom.: 885 Cov.: 32

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.0995

GnomAD4 exome AF: 0.109 AC: 146010 AN: 1335940 Hom.: 9173 Cov.: 19 AF XY: 0.111 AC XY: 74261 AN XY: 668846

African (AFR) AF: 0.0561 AC: 1710 AN: 30476

American (AMR) AF: 0.151 AC: 5867 AN: 38814

Ashkenazi Jewish (ASJ) AF: 0.0999 AC: 2466 AN: 24688

East Asian (EAS) AF: 0.267 AC: 10292 AN: 38538

South Asian (SAS) AF: 0.187 AC: 14887 AN: 79554

European-Finnish (FIN) AF: 0.121 AC: 6319 AN: 52376

Middle Eastern (MID) AF: 0.0814 AC: 403 AN: 4952

European-Non Finnish (NFE) AF: 0.0968 AC: 97798 AN: 1010566

Other (OTH) AF: 0.112 AC: 6268 AN: 55976

GnomAD4 genome AF: 0.0977 AC: 14840 AN: 151842 Hom.: 888 Cov.: 32 AF XY: 0.103 AC XY: 7611 AN XY: 74166

African (AFR) AF: 0.0577 AC: 2390 AN: 41414

American (AMR) AF: 0.125 AC: 1907 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3466

East Asian (EAS) AF: 0.252 AC: 1275 AN: 5068

South Asian (SAS) AF: 0.194 AC: 933 AN: 4810

European-Finnish (FIN) AF: 0.121 AC: 1281 AN: 10544

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0942 AC: 6402 AN: 67948

Other (OTH) AF: 0.0980 AC: 207 AN: 2112

Alfa AF: 0.0953 Hom.: 165

Bravo AF: 0.0960

Asia WGS AF: 0.184 AC: 643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.46
PhyloP100		0.17
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: rs10857748; hg19: chr10-135372310; COSMIC: COSV58219719;