20-10216438-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_040710.1(SNAP25-AS1):n.270+2799A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 151,984 control chromosomes in the GnomAD database, including 44,745 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 0.76 (44745 hom., cov: 30)
• Consequence: SNAP25-AS1 NR_040710.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

Genes affected

SNAP25-AS1 (HGNC:44312): (SNAP25 antisense RNA 1)

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP25-AS1	NR_040710.1	n.270+2799A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP25-AS1	ENST00000421143.6	n.6-19501A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115200 AN: 151864 Hom.: 44678 Cov.: 30

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.748

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

GnomAD4 genome AF: 0.759 AC: 115329 AN: 151984 Hom.: 44745 Cov.: 30 AF XY: 0.762 AC XY: 56610 AN XY: 74254

Gnomad4 AFR AF: 0.935

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.747

Alfa AF: 0.687 Hom.: 67556

Bravo AF: 0.769

Asia WGS AF: 0.734 AC: 2549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.3
Dann	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1889189; hg19: chr20-10197086;