rs3827688

Positions:

• chr10-133555754-C-T

Variant summary

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

The NM_001143764.3(SYCE1):​c.719+26G>A variant causes a intron 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: SYCE1 NM_001143764.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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=-0.71).
• 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/exons	MANE	UniProt
SYCE1	NM_001143764.3	c.719+26G>A		intron_variant		ENST00000343131.7
SYCE1	NM_001143763.2	c.719+26G>A		intron_variant
SYCE1	NM_130784.4	c.611+26G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYCE1	ENST00000343131.7	c.719+26G>A		intron_variant		1	NM_001143764.3	A2

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

GnomAD3 exomes AF: 0.127 AC: 31375 AN: 247948 Hom.: 2373 AF XY: 0.127 AC XY: 17099 AN XY: 134350

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 SAS exome AF: 0.189

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

Gnomad4 AFR exome AF: 0.0567

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.0998

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.0980

Gnomad4 OTH exome AF: 0.113

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

Gnomad4 AFR AF: 0.0579

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.0942

Gnomad4 OTH AF: 0.0980

Alfa AF: 0.0925 Hom.: 83

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3827688; hg19: chr10-135369258; COSMIC: COSV58217403;