20-10244102-G-A

Variant names:

• chr20-10244102-G-A
• rs6104571
• NM_130811.4:c.-64+25125G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_130811.4(SNAP25):​c.-64+25125G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,038 control chromosomes in the GnomAD database, including 19,902 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (19902 hom., cov: 32)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.100
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-10244102-G-A is Benign according to our data. Variant chr20-10244102-G-A is described in ClinVar as Benign. ClinVar VariationId is 1257513.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.57 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25	NM_130811.4	MANE Select	c.-64+25125G>A		intron	N/A	NP_570824.1	P60880-1
	SNAP25	NM_001322902.2		c.-64+24889G>A		intron	N/A	NP_001309831.1	P60880-2
	SNAP25	NM_001322903.2		c.-64+9765G>A		intron	N/A	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.-64+25125G>A		intron	N/A	ENSP00000254976.3	P60880-1
	SNAP25	ENST00000304886.6	TSL:1	c.-64+25125G>A		intron	N/A	ENSP00000307341.2	P60880-2
	SNAP25	ENST00000961779.1		c.-64+25125G>A		intron	N/A	ENSP00000631838.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76628 AN: 151920 Hom.: 19885 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.504 AC: 76692 AN: 152038 Hom.: 19902 Cov.: 32 AF XY: 0.498 AC XY: 37006 AN XY: 74322

African (AFR) AF: 0.424 AC: 17560 AN: 41442

American (AMR) AF: 0.487 AC: 7440 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2128 AN: 3472

East Asian (EAS) AF: 0.293 AC: 1516 AN: 5178

South Asian (SAS) AF: 0.497 AC: 2393 AN: 4814

European-Finnish (FIN) AF: 0.456 AC: 4812 AN: 10560

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39085 AN: 67988

Other (OTH) AF: 0.518 AC: 1093 AN: 2112

Alfa AF: 0.554 Hom.: 30132

Bravo AF: 0.499

Asia WGS AF: 0.400 AC: 1392 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.51
PhyloP100		-0.10
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: rs6104571; hg19: chr20-10224750;