rs498337

chr11-1833341-G-A

Variant summary

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

The ENST00000430303.5(SYT8):c.-9-1756G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,204 control chromosomes in the GnomAD database, including 5,857 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 0.27 (5857 hom., cov: 33)
• Consequence: SYT8 ENST00000430303.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

Genes affected

SYT8 (HGNC:19264): (synaptotagmin 8) This gene encodes a member of the synaptotagmin protein family. Synaptotagmins are membrane proteins that are important in neurotransmission and hormone secretion, both of which involve regulated exocytosis. Expression of the encoded protein in human pancreatic islets has been connected to activity of the promoter for the insulin gene, on the same chromosome several hundred kilobases away (PMID: 21336277 and 22928559). This association would link response to gluclose to insulin secretion. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

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 = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT8	XM_011520455.2	c.-13+1445G>A		intron_variant
SYT8	XM_011520456.3	c.-13+1445G>A		intron_variant
SYT8	XM_017018528.2	c.-10+1445G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT8	ENST00000417052.5	c.-12-1753G>A		intron_variant		3
SYT8	ENST00000430303.5	c.-9-1756G>A		intron_variant		4
SYT8	ENST00000479276.5	n.810+1445G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40727 AN: 152088 Hom.: 5858 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.313

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.268 AC: 40732 AN: 152204 Hom.: 5857 Cov.: 33 AF XY: 0.269 AC XY: 19992 AN XY: 74402

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.312

Alfa AF: 0.296 Hom.: 7818

Bravo AF: 0.273

Asia WGS AF: 0.380 AC: 1323 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	1.5
Dann	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs498337; hg19: chr11-1854571;