rs498337

Variant names:

• chr11-1833341-G-A
• rs498337
• ENST00000430303.5:c.-9-1756G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SYT8	XM_011520455.2	c.-13+1445G>A		intron_variant	Intron 1 of 8		XP_011518757.2
SYT8	XM_017018528.2	c.-10+1445G>A		intron_variant	Intron 1 of 8		XP_016874017.2
SYT8	XM_011520456.3	c.-13+1445G>A		intron_variant	Intron 1 of 7		XP_011518758.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT8	ENST00000430303.5	c.-9-1756G>A		intron_variant	Intron 2 of 4	4		ENSP00000392469.1
SYT8	ENST00000417052.5	c.-12-1753G>A		intron_variant	Intron 1 of 3	3		ENSP00000387678.1
SYT8	ENST00000479276.5	n.810+1445G>A		intron_variant	Intron 1 of 5	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

African (AFR) AF: 0.170 AC: 7064 AN: 41532

American (AMR) AF: 0.343 AC: 5243 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1045 AN: 3470

East Asian (EAS) AF: 0.524 AC: 2696 AN: 5148

South Asian (SAS) AF: 0.265 AC: 1277 AN: 4824

European-Finnish (FIN) AF: 0.213 AC: 2260 AN: 10612

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20093 AN: 67996

Other (OTH) AF: 0.312 AC: 661 AN: 2116

Alfa AF: 0.292 Hom.: 10792

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs498337; hg19: chr11-1854571;