rs8119844

Positions:

• chr20-10214030-G-A
• chr20-10214030-G-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+5207C>T 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 0.234 in 151,998 control chromosomes in the GnomAD database, including 4,460 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 0.23 (4460 hom., cov: 32)
• Consequence: SNAP25-AS1 NR_040710.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.647

Genes affected

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

LOC124904959 (HGNC:):

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAP25-AS1	NR_040710.1	n.270+5207C>T		intron_variant, non_coding_transcript_variant
LOC124904959	XR_007067723.1	n.376+175G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAP25-AS1	ENST00000421143.6	n.6-17093C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35584 AN: 151880 Hom.: 4455 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.00675

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.234 AC: 35602 AN: 151998 Hom.: 4460 Cov.: 32 AF XY: 0.227 AC XY: 16879 AN XY: 74286

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.00677

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.273

Alfa AF: 0.265 Hom.: 7454

Bravo AF: 0.233

Asia WGS AF: 0.102 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8119844; hg19: chr20-10194678;