rs41306792

Variant names:

• chr20-10275483-A-G
• rs41306792
• NM_130811.4:c.-9A>G

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 2.46
• Publications: 2 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1853 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	NM_130811.4	MANE Select	c.-9A>G		5_prime_UTR	Exon 2 of 8	NP_570824.1	P60880-1
	SNAP25	NM_001322902.2		c.-9A>G		5_prime_UTR	Exon 2 of 8	NP_001309831.1	P60880-2
	SNAP25	NM_001322903.2		c.-9A>G		5_prime_UTR	Exon 3 of 9	NP_001309832.1	P60880-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	ENST00000254976.7	TSL:1 MANE Select	c.-9A>G		5_prime_UTR	Exon 2 of 8	ENSP00000254976.3	P60880-1
	SNAP25	ENST00000304886.6	TSL:1	c.-9A>G		5_prime_UTR	Exon 2 of 8	ENSP00000307341.2	P60880-2
	SNAP25	ENST00000961779.1		c.-9A>G		5_prime_UTR	Exon 2 of 9	ENSP00000631838.1

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

GnomAD2 exomes AF: 0.00424 AC: 978 AN: 230864 AF XY: 0.00373

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 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

African (AFR) AF: 0.0392 AC: 1307 AN: 33332

American (AMR) AF: 0.00345 AC: 148 AN: 42916

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 284 AN: 25762

East Asian (EAS) AF: 0.00 AC: 0 AN: 39344

South Asian (SAS) AF: 0.000732 AC: 61 AN: 83348

European-Finnish (FIN) AF: 0.0000572 AC: 3 AN: 52490

Middle Eastern (MID) AF: 0.0116 AC: 66 AN: 5680

European-Non Finnish (NFE) AF: 0.00121 AC: 1338 AN: 1104816

Other (OTH) AF: 0.00419 AC: 251 AN: 59844

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

African (AFR) AF: 0.0383 AC: 1591 AN: 41498

American (AMR) AF: 0.00674 AC: 103 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00143 AC: 97 AN: 68010

Other (OTH) AF: 0.00853 AC: 18 AN: 2110

Alfa AF: 0.00692 Hom.: 16

Bravo AF: 0.0141

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		2.5
Mutation Taster		=293/7	polymorphism

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: rs41306792; hg19: chr20-10256131;