rs8181425

Positions:

• chr10-133556966-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000343131.7(SYCE1):​c.464+101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,478,170 control chromosomes in the GnomAD database, including 10,624 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 0.13 (1332 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9292 hom.)
• Consequence: SYCE1 ENST00000343131.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

Genes affected

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]

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYCE1	NM_001143764.3	c.464+101A>G		intron_variant		ENST00000343131.7	NP_001137236.1
SYCE1	NM_001143763.2	c.464+101A>G		intron_variant			NP_001137235.1
SYCE1	NM_130784.4	c.356+101A>G		intron_variant			NP_570140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYCE1	ENST00000343131.7	c.464+101A>G		intron_variant		1	NM_001143764.3	ENSP00000341282	A2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20318 AN: 151882 Hom.: 1329 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0946

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.111 AC: 147293 AN: 1326168 Hom.: 9292 Cov.: 20 AF XY: 0.112 AC XY: 74764 AN XY: 666268

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.0982

Gnomad4 EAS exome AF: 0.268

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.0936

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.134 AC: 20331 AN: 152002 Hom.: 1332 Cov.: 33 AF XY: 0.138 AC XY: 10226 AN XY: 74294

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.0946

Gnomad4 OTH AF: 0.124

Alfa AF: 0.114 Hom.: 141

Asia WGS AF: 0.191 AC: 669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.8
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8181425; hg19: chr10-135370470; COSMIC: COSV58216328;