rs3827688

Variant names:

• chr10-133555754-C-T
• rs3827688
• ENST00000368520.1:n.2452C>T

Variant summary

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

The ENST00000368520.1(CYP2E1):​n.2452C>T 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 0.109 in 1,609,994 control chromosomes in the GnomAD database, including 10,997 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 (900 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10097 hom.)
• Consequence: CYP2E1 ENST00000368520.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 10 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCE1	NM_001143764.3	c.719+26G>A		intron_variant	Intron 10 of 12	ENST00000343131.7	NP_001137236.1
SYCE1	NM_001143763.2	c.719+26G>A		intron_variant	Intron 10 of 12		NP_001137235.1
SYCE1	NM_130784.4	c.611+26G>A		intron_variant	Intron 10 of 12		NP_570140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYCE1	ENST00000343131.7	c.719+26G>A		intron_variant	Intron 10 of 12	1	NM_001143764.3	ENSP00000341282.5

Frequencies

GnomAD3 genomes AF: 0.0979 AC: 14884 AN: 151988 Hom.: 897 Cov.: 33

Gnomad AFR AF: 0.0580

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.0995

GnomAD2 exomes AF: 0.127 AC: 31375 AN: 247948 AF XY: 0.127

Gnomad AFR exome AF: 0.0571

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.0976

Gnomad EAS exome AF: 0.254

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.0936

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.110 AC: 160414 AN: 1457888 Hom.: 10097 Cov.: 35 AF XY: 0.112 AC XY: 80912 AN XY: 725364

African (AFR) AF: 0.0567 AC: 1896 AN: 33462

American (AMR) AF: 0.154 AC: 6878 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.0998 AC: 2603 AN: 26070

East Asian (EAS) AF: 0.267 AC: 10601 AN: 39684

South Asian (SAS) AF: 0.188 AC: 16218 AN: 86160

European-Finnish (FIN) AF: 0.120 AC: 5999 AN: 50198

Middle Eastern (MID) AF: 0.0831 AC: 479 AN: 5764

European-Non Finnish (NFE) AF: 0.0980 AC: 108929 AN: 1111540

Other (OTH) AF: 0.113 AC: 6811 AN: 60330

GnomAD4 genome AF: 0.0979 AC: 14891 AN: 152106 Hom.: 900 Cov.: 33 AF XY: 0.103 AC XY: 7645 AN XY: 74312

African (AFR) AF: 0.0579 AC: 2403 AN: 41500

American (AMR) AF: 0.125 AC: 1916 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1298 AN: 5142

South Asian (SAS) AF: 0.194 AC: 930 AN: 4802

European-Finnish (FIN) AF: 0.121 AC: 1286 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0942 AC: 6404 AN: 67974

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

Alfa AF: 0.0911 Hom.: 84

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	-0.71
CADD	Benign	7.6
DANN	Benign	0.77
PhyloP100		-0.065
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3827688; hg19: chr10-135369258; COSMIC: COSV58217403;