chr20-10278006-C-A

Variant names:

• chr20-10278006-C-A
• rs6039806
• NM_130811.4:c.114+280C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130811.4(SNAP25):​c.114+280C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 295,836 control chromosomes in the GnomAD database, including 43,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24630 hom., cov: 33)
  • Exomes 𝑓: 0.51 (18794 hom.)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.277
• Publications: 8 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-10278006-C-A is Benign according to our data. Variant chr20-10278006-C-A is described in ClinVar as Benign. ClinVar VariationId is 1294565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130811.4. 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	NM_130811.4	MANE Select	c.114+280C>A		intron	N/A	NP_570824.1
	SNAP25	NM_001322902.2		c.114+280C>A		intron	N/A	NP_001309831.1
	SNAP25	NM_001322903.2		c.114+280C>A		intron	N/A	NP_001309832.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	ENST00000254976.7	TSL:1 MANE Select	c.114+280C>A		intron	N/A	ENSP00000254976.3
	SNAP25	ENST00000304886.6	TSL:1	c.114+280C>A		intron	N/A	ENSP00000307341.2
	SNAP25	ENST00000492814.1	TSL:2	n.367C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84621 AN: 151944 Hom.: 24578 Cov.: 33

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.547

GnomAD4 exome AF: 0.509 AC: 73123 AN: 143774 Hom.: 18794 Cov.: 0 AF XY: 0.507 AC XY: 37241 AN XY: 73404

African (AFR) AF: 0.733 AC: 3574 AN: 4876

American (AMR) AF: 0.562 AC: 2653 AN: 4720

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 3147 AN: 5608

East Asian (EAS) AF: 0.457 AC: 5459 AN: 11946

South Asian (SAS) AF: 0.467 AC: 1632 AN: 3498

European-Finnish (FIN) AF: 0.509 AC: 4651 AN: 9136

Middle Eastern (MID) AF: 0.579 AC: 416 AN: 718

European-Non Finnish (NFE) AF: 0.497 AC: 46434 AN: 93444

Other (OTH) AF: 0.525 AC: 5157 AN: 9828

GnomAD4 genome AF: 0.557 AC: 84734 AN: 152062 Hom.: 24630 Cov.: 33 AF XY: 0.555 AC XY: 41267 AN XY: 74324

African (AFR) AF: 0.728 AC: 30208 AN: 41500

American (AMR) AF: 0.540 AC: 8257 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1928 AN: 3468

East Asian (EAS) AF: 0.371 AC: 1918 AN: 5164

South Asian (SAS) AF: 0.438 AC: 2117 AN: 4828

European-Finnish (FIN) AF: 0.500 AC: 5274 AN: 10558

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33308 AN: 67944

Other (OTH) AF: 0.542 AC: 1143 AN: 2110

Alfa AF: 0.549 Hom.: 3815

Bravo AF: 0.569

Asia WGS AF: 0.418 AC: 1454 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 08, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.48
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6039806; hg19: chr20-10258654;