rs362987

Positions:

• chr20-10296804-A-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_130811.4(SNAP25):​c.282-121A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 1,463,396 control chromosomes in the GnomAD database, including 172,744 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20130 hom., cov: 33)
  • Exomes 𝑓: 0.48 (152614 hom.)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.65

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 20-10296804-A-C is Benign according to our data. Variant chr20-10296804-A-C is described in ClinVar as [Benign]. Clinvar id is 1246499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.282-121A>C		intron_variant		ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.282-121A>C		intron_variant		1	NM_130811.4	ENSP00000254976	P5
SNAP25-AS1	ENST00000421143.6	n.5+71911T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77500 AN: 151956 Hom.: 20090 Cov.: 33

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.515

GnomAD4 exome AF: 0.480 AC: 629680 AN: 1311322 Hom.: 152614 Cov.: 18 AF XY: 0.480 AC XY: 312426 AN XY: 651024

Gnomad4 AFR exome AF: 0.573

Gnomad4 AMR exome AF: 0.535

Gnomad4 ASJ exome AF: 0.551

Gnomad4 EAS exome AF: 0.363

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.494

Gnomad4 NFE exome AF: 0.479

Gnomad4 OTH exome AF: 0.480

GnomAD4 genome AF: 0.510 AC: 77602 AN: 152074 Hom.: 20130 Cov.: 33 AF XY: 0.509 AC XY: 37820 AN XY: 74328

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.509

Alfa AF: 0.512 Hom.: 5765

Bravo AF: 0.517

Asia WGS AF: 0.380 AC: 1321 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 08, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.78

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: rs362987; hg19: chr20-10277452; COSMIC: COSV54775524; COSMIC: COSV54775524;