20-10214785-T-G

Variant names:

• chr20-10214785-T-G
• rs6104567
• ENST00000421143.7:n.133-17848A>C

Variant summary

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

The ENST00000421143.7(SNAP25-AS1):​n.133-17848A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,122 control chromosomes in the GnomAD database, including 6,211 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 0.27 (6211 hom., cov: 33)
• Consequence: SNAP25-AS1 ENST00000421143.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• 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: 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

ENSG00000232448 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000421143.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25-AS1	NR_040710.1		n.270+4452A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25-AS1	ENST00000421143.7	TSL:5	n.133-17848A>C		intron	N/A
	SNAP25-AS1	ENST00000426491.5	TSL:5	n.270+4452A>C		intron	N/A
	SNAP25-AS1	ENST00000451151.7	TSL:2	n.301+4452A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40431 AN: 152002 Hom.: 6194 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.266 AC: 40466 AN: 152122 Hom.: 6211 Cov.: 33 AF XY: 0.279 AC XY: 20715 AN XY: 74364

African (AFR) AF: 0.151 AC: 6262 AN: 41512

American (AMR) AF: 0.403 AC: 6162 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3472

East Asian (EAS) AF: 0.547 AC: 2827 AN: 5172

South Asian (SAS) AF: 0.378 AC: 1825 AN: 4822

European-Finnish (FIN) AF: 0.387 AC: 4089 AN: 10576

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17768 AN: 67958

Other (OTH) AF: 0.271 AC: 572 AN: 2112

Alfa AF: 0.261 Hom.: 12628

Bravo AF: 0.266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.65
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs6104567; hg19: chr20-10195433;