20-10282928-A-G

Variant names:

• chr20-10282928-A-G
• rs6039807
• NM_130811.4:c.115-1796A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130811.4(SNAP25):​c.115-1796A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,126 control chromosomes in the GnomAD database, including 22,624 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 0.54 (22624 hom., cov: 33)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.790
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

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.115-1796A>G		intron	N/A	NP_570824.1	P60880-1
	SNAP25	NM_001322902.2		c.115-1796A>G		intron	N/A	NP_001309831.1	P60880-2
	SNAP25	NM_001322903.2		c.115-1796A>G		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.115-1796A>G		intron	N/A	ENSP00000254976.3	P60880-1
	SNAP25	ENST00000304886.6	TSL:1	c.115-1796A>G		intron	N/A	ENSP00000307341.2	P60880-2
	SNAP25	ENST00000961779.1		c.115-1796A>G		intron	N/A	ENSP00000631838.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81766 AN: 152008 Hom.: 22582 Cov.: 33

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.538 AC: 81866 AN: 152126 Hom.: 22624 Cov.: 33 AF XY: 0.536 AC XY: 39899 AN XY: 74390

African (AFR) AF: 0.655 AC: 27173 AN: 41504

American (AMR) AF: 0.536 AC: 8181 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1935 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1896 AN: 5176

South Asian (SAS) AF: 0.434 AC: 2093 AN: 4826

European-Finnish (FIN) AF: 0.499 AC: 5287 AN: 10596

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33605 AN: 67970

Other (OTH) AF: 0.530 AC: 1118 AN: 2108

Alfa AF: 0.511 Hom.: 16483

Bravo AF: 0.548

Asia WGS AF: 0.404 AC: 1402 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.9
DANN	Benign	0.62
PhyloP100		0.79
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: rs6039807; hg19: chr20-10263576;