rs115753500

Variant names:

• chr20-10275143-C-T
• rs115753500
• NM_130811.4:c.-63-286C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_130811.4(SNAP25):​c.-63-286C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 151,794 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.017 (51 hom., cov: 32)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00700
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-10275143-C-T is Benign according to our data. Variant chr20-10275143-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1300470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0168 (2544/151794) while in subpopulation AFR AF = 0.034 (1409/41442). AF 95% confidence interval is 0.0325. There are 51 homozygotes in GnomAd4. There are 1232 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2544 AD gene.

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.-63-286C>T		intron	N/A	NP_570824.1	P60880-1
	SNAP25	NM_001322902.2		c.-63-286C>T		intron	N/A	NP_001309831.1	P60880-2
	SNAP25	NM_001322903.2		c.-63-286C>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.-63-286C>T		intron	N/A	ENSP00000254976.3	P60880-1
	SNAP25	ENST00000304886.6	TSL:1	c.-63-286C>T		intron	N/A	ENSP00000307341.2	P60880-2
	SNAP25	ENST00000961779.1		c.-63-286C>T		intron	N/A	ENSP00000631838.1

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 2538 AN: 151676 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00546

Gnomad FIN AF: 0.00958

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0100

Gnomad OTH AF: 0.0154

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

GnomAD4 genome AF: 0.0168 AC: 2544 AN: 151794 Hom.: 51 Cov.: 32 AF XY: 0.0166 AC XY: 1232 AN XY: 74182

African (AFR) AF: 0.0340 AC: 1409 AN: 41442

American (AMR) AF: 0.0128 AC: 195 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3462

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.00567 AC: 27 AN: 4762

European-Finnish (FIN) AF: 0.00958 AC: 101 AN: 10546

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0100 AC: 680 AN: 67864

Other (OTH) AF: 0.0152 AC: 32 AN: 2104

Alfa AF: 0.0187 Hom.: 15

Bravo AF: 0.0175

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.64
PhyloP100		-0.0070
Mutation Taster		=100/0	polymorphism

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: rs115753500; hg19: chr20-10255791;