rs41306792

chr20-10275483-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_130811.4(SNAP25):c.-9A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,599,682 control chromosomes in the GnomAD database, including 68 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (30 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (38 hom.)
• Consequence: SNAP25 NM_130811.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.46

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

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 20-10275483-A-G is Benign according to our data. Variant chr20-10275483-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 448434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1853/152150) while in subpopulation AFR AF= 0.0383 (1591/41498). AF 95% confidence interval is 0.0368. There are 30 homozygotes in gnomad4. There are 856 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1852 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP25	NM_130811.4	c.-9A>G		5_prime_UTR_variant	2/8	ENST00000254976.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP25	ENST00000254976.7	c.-9A>G		5_prime_UTR_variant	2/8	1	NM_130811.4	P5
SNAP25-AS1	ENST00000421143.6	n.6-78546T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1852 AN: 152032 Hom.: 29 Cov.: 33

Gnomad AFR AF: 0.0384

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00675

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.00862

GnomAD3 exomes AF: 0.00424 AC: 978 AN: 230864 Hom.: 8 AF XY: 0.00373 AC XY: 463 AN XY: 124256

Gnomad AFR exome AF: 0.0397

Gnomad AMR exome AF: 0.00312

Gnomad ASJ exome AF: 0.0107

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000687

Gnomad FIN exome AF: 0.0000511

Gnomad NFE exome AF: 0.00161

Gnomad OTH exome AF: 0.00315

GnomAD4 exome AF: 0.00239 AC: 3458 AN: 1447532 Hom.: 38 Cov.: 30 AF XY: 0.00235 AC XY: 1687 AN XY: 718730

Gnomad4 AFR exome AF: 0.0392

Gnomad4 AMR exome AF: 0.00345

Gnomad4 ASJ exome AF: 0.0110

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000732

Gnomad4 FIN exome AF: 0.0000572

Gnomad4 NFE exome AF: 0.00121

Gnomad4 OTH exome AF: 0.00419

GnomAD4 genome AF: 0.0122 AC: 1853 AN: 152150 Hom.: 30 Cov.: 33 AF XY: 0.0115 AC XY: 856 AN XY: 74368

Gnomad4 AFR AF: 0.0383

Gnomad4 AMR AF: 0.00674

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00143

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.00693 Hom.: 13

Bravo AF: 0.0141

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jun 21, 2017

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 28, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.060
Cadd	Benign	13
Dann	Benign	0.93

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

Publications

LitVar

Other links and lift over

dbSNP: rs41306792; hg19: chr20-10256131;