dbSNP rs8119844: SNAP25-AS1:n.133-17093C>T (chr20-10214030-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000421143.7(SNAP25-AS1):n.133-17093C>T variant causes a intron 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
ENST00000421143.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.647

Publications

8 publications found

Variant links:

Genes affected

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

SNAP25-AS1 links:

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 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, ClinGen
congenital myasthenic syndrome 18
Inheritance: AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
presynaptic congenital myasthenic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SNAP25 links:

ENSG00000232448 (HGNC:):

ENSG00000232448 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SNAP25-AS1	NR_040710.1 link	n.270+5207C>T		intron_variant	Intron 1 of 4
LOC124904959	XR_007067723.1 link	n.376+175G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
SNAP25-AS1	ENST00000421143.7 link	n.133-17093C>T	intron_variant	Intron 1 of 3	5
SNAP25-AS1	ENST00000426491.5 link	n.270+5207C>T	intron_variant	Intron 1 of 4	5
SNAP25-AS1	ENST00000451151.7 link	n.301+5207C>T	intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35584

AN:

151880

Hom.:

4455

Cov.:

show subpopulations

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.:

AF XY:

0.227

AC XY:

16879

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.211

AC:

8745

AN:

41468

American (AMR)

AF:

0.204

AC:

3122

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

1304

AN:

3468

East Asian (EAS)

AF:

0.00677

AC:

AN:

5172

South Asian (SAS)

AF:

0.182

AC:

877

AN:

4808

European-Finnish (FIN)

AF:

0.173

AC:

1832

AN:

10562

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.277

AC:

18825

AN:

67940

Other (OTH)

AF:

0.273

AC:

575

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1380

2760

4141

5521

6901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.260

Hom.:

10117

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

(source)

DANN

Benign

0.62

PhyloP100

0.65

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over