rs6074113

Variant names:

• chr20-10261363-A-C
• rs6074113
• NM_130811.4:c.-63-14066A>C

Variant summary

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

The NM_130811.4(SNAP25):​c.-63-14066A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,850 control chromosomes in the GnomAD database, including 19,288 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 0.50 (19288 hom., cov: 31)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 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.-63-14066A>C		intron	N/A	NP_570824.1	P60880-1
	SNAP25	NM_001322902.2		c.-63-14066A>C		intron	N/A	NP_001309831.1	P60880-2
	SNAP25	NM_001322903.2		c.-63-14066A>C		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.-63-14066A>C		intron	N/A	ENSP00000254976.3	P60880-1
	SNAP25	ENST00000304886.6	TSL:1	c.-63-14066A>C		intron	N/A	ENSP00000307341.2	P60880-2
	SNAP25	ENST00000961779.1		c.-63-14066A>C		intron	N/A	ENSP00000631838.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75613 AN: 151732 Hom.: 19276 Cov.: 31

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.498 AC: 75673 AN: 151850 Hom.: 19288 Cov.: 31 AF XY: 0.500 AC XY: 37105 AN XY: 74194

African (AFR) AF: 0.579 AC: 23992 AN: 41412

American (AMR) AF: 0.446 AC: 6809 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1316 AN: 3468

East Asian (EAS) AF: 0.690 AC: 3561 AN: 5158

South Asian (SAS) AF: 0.639 AC: 3059 AN: 4788

European-Finnish (FIN) AF: 0.482 AC: 5079 AN: 10528

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30167 AN: 67928

Other (OTH) AF: 0.483 AC: 1021 AN: 2112

Alfa AF: 0.464 Hom.: 49988

Bravo AF: 0.498

Asia WGS AF: 0.657 AC: 2282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.56
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6074113; hg19: chr20-10242011;