20-10286622-A-G

Variant names:

• chr20-10286622-A-G
• rs6108461
• NM_130811.4:c.163+1850A>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.163+1850A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,950 control chromosomes in the GnomAD database, including 24,862 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 0.56 (24862 hom., cov: 32)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.163+1850A>G		intron_variant	Intron 4 of 7	ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.163+1850A>G		intron_variant	Intron 4 of 7	1	NM_130811.4	ENSP00000254976.3

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84970 AN: 151832 Hom.: 24808 Cov.: 32

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.560 AC: 85085 AN: 151950 Hom.: 24862 Cov.: 32 AF XY: 0.558 AC XY: 41405 AN XY: 74260

African (AFR) AF: 0.730 AC: 30225 AN: 41424

American (AMR) AF: 0.546 AC: 8342 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1939 AN: 3466

East Asian (EAS) AF: 0.370 AC: 1904 AN: 5152

South Asian (SAS) AF: 0.433 AC: 2091 AN: 4828

European-Finnish (FIN) AF: 0.498 AC: 5258 AN: 10548

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33601 AN: 67944

Other (OTH) AF: 0.546 AC: 1152 AN: 2110

Alfa AF: 0.470 Hom.: 1954

Bravo AF: 0.573

Asia WGS AF: 0.410 AC: 1426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.45
DANN	Benign	0.45
PhyloP100		-1.6
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: rs6108461; hg19: chr20-10267270;