rs6039806

Positions:

• chr20-10278006-C-A
• chr20-10278006-C-G
• chr20-10278006-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000254976.7(SNAP25):​c.114+280C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 295,836 control chromosomes in the GnomAD database, including 43,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24630 hom., cov: 33)
  • Exomes 𝑓: 0.51 (18794 hom.)
• Consequence: SNAP25 ENST00000254976.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.277

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-10278006-C-A is Benign according to our data. Variant chr20-10278006-C-A is described in ClinVar as [Benign]. Clinvar id is 1294565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.114+280C>A		intron_variant		ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.114+280C>A		intron_variant		1	NM_130811.4	ENSP00000254976	P5
SNAP25-AS1	ENST00000421143.6	n.6-81069G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84621 AN: 151944 Hom.: 24578 Cov.: 33

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.547

GnomAD4 exome AF: 0.509 AC: 73123 AN: 143774 Hom.: 18794 Cov.: 0 AF XY: 0.507 AC XY: 37241 AN XY: 73404

Gnomad4 AFR exome AF: 0.733

Gnomad4 AMR exome AF: 0.562

Gnomad4 ASJ exome AF: 0.561

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.467

Gnomad4 FIN exome AF: 0.509

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.525

GnomAD4 genome AF: 0.557 AC: 84734 AN: 152062 Hom.: 24630 Cov.: 33 AF XY: 0.555 AC XY: 41267 AN XY: 74324

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.542

Alfa AF: 0.543 Hom.: 3613

Bravo AF: 0.569

Asia WGS AF: 0.418 AC: 1454 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 08, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.48

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: rs6039806; hg19: chr20-10258654;