NM_130811.4:c.-64+13470C>T

Variant names:

• chr20-10232447-C-T
• rs2423487
• NM_130811.4:c.-64+13470C>T

Variant summary

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

The NM_130811.4(SNAP25):​c.-64+13470C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,246 control chromosomes in the GnomAD database, including 60,587 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 0.89 (60587 hom., cov: 32)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.807
• Publications: 9 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.-64+13470C>T		intron_variant	Intron 1 of 7	ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.-64+13470C>T		intron_variant	Intron 1 of 7	1	NM_130811.4	ENSP00000254976.3

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135634 AN: 152128 Hom.: 60533 Cov.: 32

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.892 AC: 135751 AN: 152246 Hom.: 60587 Cov.: 32 AF XY: 0.891 AC XY: 66350 AN XY: 74438

African (AFR) AF: 0.880 AC: 36537 AN: 41542

American (AMR) AF: 0.907 AC: 13865 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3161 AN: 3472

East Asian (EAS) AF: 0.830 AC: 4292 AN: 5168

South Asian (SAS) AF: 0.885 AC: 4268 AN: 4820

European-Finnish (FIN) AF: 0.859 AC: 9113 AN: 10608

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.904 AC: 61519 AN: 68026

Other (OTH) AF: 0.905 AC: 1914 AN: 2116

Alfa AF: 0.903 Hom.: 260137

Bravo AF: 0.894

Asia WGS AF: 0.876 AC: 3046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.56
DANN	Benign	0.53
PhyloP100		-0.81
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: rs2423487; hg19: chr20-10213095;