rs362987

Variant names:

• chr20-10296804-A-C
• rs362987
• NM_130811.4:c.282-121A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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 -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 VariationId 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 rank	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.282-121A>C		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.282-121A>C		intron_variant	Intron 5 of 7	1	NM_130811.4	ENSP00000254976.3

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

African (AFR) AF: 0.573 AC: 17400 AN: 30356

American (AMR) AF: 0.535 AC: 20339 AN: 38006

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 12099 AN: 21942

East Asian (EAS) AF: 0.363 AC: 13883 AN: 38228

South Asian (SAS) AF: 0.459 AC: 33438 AN: 72918

European-Finnish (FIN) AF: 0.494 AC: 19500 AN: 39482

Middle Eastern (MID) AF: 0.576 AC: 2151 AN: 3734

European-Non Finnish (NFE) AF: 0.479 AC: 484498 AN: 1011752

Other (OTH) AF: 0.480 AC: 26372 AN: 54904

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

African (AFR) AF: 0.570 AC: 23638 AN: 41484

American (AMR) AF: 0.525 AC: 8028 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1929 AN: 3472

East Asian (EAS) AF: 0.297 AC: 1532 AN: 5154

South Asian (SAS) AF: 0.433 AC: 2080 AN: 4800

European-Finnish (FIN) AF: 0.495 AC: 5239 AN: 10582

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33507 AN: 67980

Other (OTH) AF: 0.509 AC: 1076 AN: 2112

Alfa AF: 0.504 Hom.: 8845

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

Mar 08, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.78
PhyloP100		1.6
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: rs362987; hg19: chr20-10277452; COSMIC: COSV54775524; COSMIC: COSV54775524;