rs363021

Variant names:

• chr20-10261163-C-T
• rs363021
• NM_130811.4:c.-63-14266C>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.-63-14266C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,856 control chromosomes in the GnomAD database, including 17,832 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 0.48 (17832 hom., cov: 31)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.-63-14266C>T		intron_variant	Intron 1 of 7	ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.-63-14266C>T		intron_variant	Intron 1 of 7	1	NM_130811.4	ENSP00000254976.3

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72949 AN: 151738 Hom.: 17823 Cov.: 31

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.481 AC: 72996 AN: 151856 Hom.: 17832 Cov.: 31 AF XY: 0.483 AC XY: 35826 AN XY: 74184

African (AFR) AF: 0.520 AC: 21513 AN: 41392

American (AMR) AF: 0.441 AC: 6724 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1282 AN: 3470

East Asian (EAS) AF: 0.692 AC: 3571 AN: 5164

South Asian (SAS) AF: 0.637 AC: 3052 AN: 4792

European-Finnish (FIN) AF: 0.483 AC: 5090 AN: 10534

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30098 AN: 67946

Other (OTH) AF: 0.471 AC: 993 AN: 2110

Alfa AF: 0.444 Hom.: 3101

Bravo AF: 0.478

Asia WGS AF: 0.652 AC: 2264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.82
DANN	Benign	0.32
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs363021; hg19: chr20-10241811;