20-10305665-A-C

Variant names:

• chr20-10305665-A-C
• rs4813925
• NM_130811.4:c.553-464A>C

Variant summary

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

The ENST00000254976.7(SNAP25):​c.553-464A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 151,988 control chromosomes in the GnomAD database, including 37,926 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 0.70 (37926 hom., cov: 31)
• Consequence: SNAP25 ENST00000254976.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000254976.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	NM_130811.4	MANE Select	c.553-464A>C		intron	N/A	NP_570824.1
	SNAP25	NM_001322902.2		c.553-464A>C		intron	N/A	NP_001309831.1
	SNAP25	NM_001322903.2		c.553-464A>C		intron	N/A	NP_001309832.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	ENST00000254976.7	TSL:1 MANE Select	c.553-464A>C		intron	N/A	ENSP00000254976.3
	SNAP25	ENST00000304886.6	TSL:1	c.553-464A>C		intron	N/A	ENSP00000307341.2
	SNAP25	ENST00000685131.1		c.553-464A>C		intron	N/A	ENSP00000508837.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106783 AN: 151870 Hom.: 37881 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.703 AC: 106889 AN: 151988 Hom.: 37926 Cov.: 31 AF XY: 0.706 AC XY: 52459 AN XY: 74276

African (AFR) AF: 0.804 AC: 33309 AN: 41452

American (AMR) AF: 0.722 AC: 11025 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2476 AN: 3472

East Asian (EAS) AF: 0.771 AC: 3963 AN: 5142

South Asian (SAS) AF: 0.721 AC: 3474 AN: 4820

European-Finnish (FIN) AF: 0.668 AC: 7050 AN: 10554

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43455 AN: 67964

Other (OTH) AF: 0.667 AC: 1405 AN: 2106

Alfa AF: 0.657 Hom.: 51494

Bravo AF: 0.709

Asia WGS AF: 0.705 AC: 2452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.63
DANN	Benign	0.50
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4813925; hg19: chr20-10286313;