rs362990

Variant names:

• chr20-10295573-A-T
• rs362990
• NM_130811.4:c.282-1352A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130811.4(SNAP25):​c.282-1352A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,966 control chromosomes in the GnomAD database, including 4,447 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 0.23 (4447 hom., cov: 32)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.282-1352A>T		intron_variant	Intron 5 of 7	ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.282-1352A>T		intron_variant	Intron 5 of 7	1	NM_130811.4	ENSP00000254976.3

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35258 AN: 151846 Hom.: 4447 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.232 AC: 35265 AN: 151966 Hom.: 4447 Cov.: 32 AF XY: 0.232 AC XY: 17194 AN XY: 74258

African (AFR) AF: 0.148 AC: 6127 AN: 41450

American (AMR) AF: 0.205 AC: 3136 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1093 AN: 3466

East Asian (EAS) AF: 0.109 AC: 561 AN: 5140

South Asian (SAS) AF: 0.229 AC: 1104 AN: 4816

European-Finnish (FIN) AF: 0.272 AC: 2864 AN: 10538

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19517 AN: 67966

Other (OTH) AF: 0.234 AC: 494 AN: 2108

Alfa AF: 0.262 Hom.: 675

Bravo AF: 0.222

Asia WGS AF: 0.159 AC: 553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.77
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs362990; hg19: chr20-10276221;