rs362988

chr20-10300722-G-A

Variant summary

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

The NM_130811.4(SNAP25):c.552+1310G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,062 control chromosomes in the GnomAD database, including 27,635 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 0.58 (27635 hom., cov: 32)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601

Genes affected

SNAP25 (HGNC:11132): (synaptosome associated protein 25) Synaptic vesicle membrane docking and fusion is mediated by SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) located on the vesicle membrane (v-SNAREs) and the target membrane (t-SNAREs). The assembled v-SNARE/t-SNARE complex consists of a bundle of four helices, one of which is supplied by v-SNARE and the other three by t-SNARE. For t-SNAREs on the plasma membrane, the protein syntaxin supplies one helix and the protein encoded by this gene contributes the other two. Therefore, this gene product is a presynaptic plasma membrane protein involved in the regulation of neurotransmitter release. Two alternative transcript variants encoding different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

SNAP25-AS1 (HGNC:44312): (SNAP25 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP25	NM_130811.4	c.552+1310G>A		intron_variant		ENST00000254976.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP25	ENST00000254976.7	c.552+1310G>A		intron_variant		1	NM_130811.4	P5
SNAP25-AS1	ENST00000421143.6	n.5+67993C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87611 AN: 151942 Hom.: 27578 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.577 AC: 87737 AN: 152062 Hom.: 27635 Cov.: 32 AF XY: 0.580 AC XY: 43099 AN XY: 74328

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.544

Alfa AF: 0.462 Hom.: 26179

Bravo AF: 0.592

Asia WGS AF: 0.485 AC: 1688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.18
Dann	Benign	0.37

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: rs362988; hg19: chr20-10281370;