rs6039769

chr20-10218306-A-Cchr20-10218306-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_040710.1(SNAP25-AS1):n.270+931T>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 0.766 in 151,816 control chromosomes in the GnomAD database, including 45,503 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 0.77 (45503 hom., cov: 29)
• Consequence: SNAP25-AS1 NR_040710.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.678

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP25-AS1	NR_040710.1	n.270+931T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP25-AS1	ENST00000421143.6	n.6-21369T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116180 AN: 151698 Hom.: 45444 Cov.: 29

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.748

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

GnomAD4 genome AF: 0.766 AC: 116300 AN: 151816 Hom.: 45503 Cov.: 29 AF XY: 0.771 AC XY: 57170 AN XY: 74160

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.780

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.748

Alfa AF: 0.681 Hom.: 40621

Bravo AF: 0.777

Asia WGS AF: 0.767 AC: 2665 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	15
Dann	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6039769; hg19: chr20-10198954;