rs362547

Variant names:

• chr20-10264491-C-T
• rs362547
• NM_130811.4:c.-63-10938C>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.-63-10938C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,000 control chromosomes in the GnomAD database, including 11,031 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 0.37 (11031 hom., cov: 31)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130811.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	NM_130811.4	MANE Select	c.-63-10938C>T		intron	N/A	NP_570824.1	P60880-1
	SNAP25	NM_001322902.2		c.-63-10938C>T		intron	N/A	NP_001309831.1	P60880-2
	SNAP25	NM_001322903.2		c.-63-10938C>T		intron	N/A	NP_001309832.1	P60880-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	ENST00000254976.7	TSL:1 MANE Select	c.-63-10938C>T		intron	N/A	ENSP00000254976.3	P60880-1
	SNAP25	ENST00000304886.6	TSL:1	c.-63-10938C>T		intron	N/A	ENSP00000307341.2	P60880-2
	SNAP25	ENST00000961779.1		c.-63-10938C>T		intron	N/A	ENSP00000631838.1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56520 AN: 151882 Hom.: 11031 Cov.: 31

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.372 AC: 56553 AN: 152000 Hom.: 11031 Cov.: 31 AF XY: 0.369 AC XY: 27445 AN XY: 74292

African (AFR) AF: 0.283 AC: 11731 AN: 41432

American (AMR) AF: 0.404 AC: 6164 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1819 AN: 3470

East Asian (EAS) AF: 0.148 AC: 766 AN: 5166

South Asian (SAS) AF: 0.272 AC: 1311 AN: 4824

European-Finnish (FIN) AF: 0.377 AC: 3977 AN: 10556

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29432 AN: 67960

Other (OTH) AF: 0.402 AC: 850 AN: 2112

Alfa AF: 0.392 Hom.: 1714

Bravo AF: 0.372

Asia WGS AF: 0.220 AC: 764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.8
DANN	Benign	0.70
PhyloP100		-0.44
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: rs362547; hg19: chr20-10245139;