rs363012

Positions:

• chr20-10239151-A-G

Variant summary

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

The NM_130811.4(SNAP25):​c.-64+20174A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,064 control chromosomes in the GnomAD database, including 12,024 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 0.39 (12024 hom., cov: 32)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.-64+20174A>G		intron_variant		ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.-64+20174A>G		intron_variant		1	NM_130811.4	ENSP00000254976	P5
SNAP25-AS1	ENST00000421143.6	n.6-42214T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58476 AN: 151946 Hom.: 12002 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.385 AC: 58546 AN: 152064 Hom.: 12024 Cov.: 32 AF XY: 0.381 AC XY: 28333 AN XY: 74344

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.370

Alfa AF: 0.344 Hom.: 12636

Bravo AF: 0.392

Asia WGS AF: 0.358 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.3
DANN	Benign	0.71

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: rs363012; hg19: chr20-10219799;