20-10216438-T-C

Variant names:

• chr20-10216438-T-C
• rs1889189
• ENST00000421143.7:n.133-19501A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000451151.7(SNAP25-AS1):​n.301+2799A>G variant causes a intron 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 ENST00000451151.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 11 publications found

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]

SNAP25 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen, Ambry Genetics
• congenital myasthenic syndrome 18

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• presynaptic congenital myasthenic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000451151.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25-AS1	NR_040710.1		n.270+2799A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25-AS1	ENST00000421143.7	TSL:5	n.133-19501A>G		intron	N/A
	SNAP25-AS1	ENST00000426491.5	TSL:5	n.270+2799A>G		intron	N/A
	SNAP25-AS1	ENST00000451151.7	TSL:2	n.301+2799A>G		intron	N/A

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

African (AFR) AF: 0.935 AC: 38808 AN: 41514

American (AMR) AF: 0.760 AC: 11614 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2546 AN: 3470

East Asian (EAS) AF: 0.729 AC: 3740 AN: 5130

South Asian (SAS) AF: 0.691 AC: 3331 AN: 4820

European-Finnish (FIN) AF: 0.729 AC: 7674 AN: 10526

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.667 AC: 45303 AN: 67934

Other (OTH) AF: 0.747 AC: 1576 AN: 2110

Alfa AF: 0.700 Hom.: 150937

Bravo AF: 0.769

Asia WGS AF: 0.734 AC: 2549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
DANN	Benign	0.70
PhyloP100		0.048

Splicing

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

Other links and lift over

dbSNP: rs1889189; hg19: chr20-10197086;