rs10857748

Positions:

• chr10-133558806-T-C

Variant summary

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

The NM_001143764.3(SYCE1):​c.271+71A>G variant causes a intron 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: SYCE1 NM_001143764.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SYCE1	NM_001143764.3	c.271+71A>G		intron_variant		ENST00000343131.7	NP_001137236.1
SYCE1	NM_001143763.2	c.271+71A>G		intron_variant			NP_001137235.1
SYCE1	NM_130784.4	c.163+71A>G		intron_variant			NP_570140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYCE1	ENST00000343131.7	c.271+71A>G		intron_variant		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

Gnomad4 AFR exome AF: 0.0561

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.0999

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.0968

Gnomad4 OTH exome AF: 0.112

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

Gnomad4 AFR AF: 0.0577

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: 0.0963 Hom.: 164

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10857748; hg19: chr10-135372310; COSMIC: COSV58219719;