rs217290

Variant names:

• chr6-83688846-C-T
• rs217290
• NM_001242792.2:c.130+18952G>A

Variant summary

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

The NM_001242792.2(SNAP91):​c.130+18952G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,880 control chromosomes in the GnomAD database, including 11,500 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 0.38 (11500 hom., cov: 31)
• Consequence: SNAP91 NM_001242792.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666
• Publications: 5 publications found

Genes affected

SNAP91 (HGNC:14986): (synaptosome associated protein 91) Predicted to enable several functions, including SNARE binding activity; clathrin binding activity; and phosphatidylinositol binding activity. Acts upstream of or within regulation of clathrin-dependent endocytosis. Predicted to be located in several cellular components, including postsynaptic density; presynaptic endosome; and presynaptic membrane. Predicted to be extrinsic component of endosome membrane. Predicted to be active in several cellular components, including Schaffer collateral - CA1 synapse; cytoplasmic vesicle; and parallel fiber to Purkinje cell synapse. Predicted to be extrinsic component of presynaptic endocytic zone membrane. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242792.2. 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
	SNAP91	NM_001242792.2	MANE Select	c.130+18952G>A		intron	N/A	NP_001229721.1	O60641-1
	SNAP91	NM_014841.3		c.130+18952G>A		intron	N/A	NP_055656.1	O60641-1
	SNAP91	NM_001376675.1		c.130+18952G>A		intron	N/A	NP_001363604.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP91	ENST00000369694.7	TSL:5 MANE Select	c.130+18952G>A		intron	N/A	ENSP00000358708.2	O60641-1
	SNAP91	ENST00000520302.5	TSL:1	c.130+18952G>A		intron	N/A	ENSP00000428511.1	O60641-4
	SNAP91	ENST00000520213.5	TSL:1	c.130+18952G>A		intron	N/A	ENSP00000428026.1	O60641-3

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57833 AN: 151762 Hom.: 11492 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.381 AC: 57865 AN: 151880 Hom.: 11500 Cov.: 31 AF XY: 0.384 AC XY: 28499 AN XY: 74206

African (AFR) AF: 0.262 AC: 10857 AN: 41438

American (AMR) AF: 0.369 AC: 5635 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1227 AN: 3468

East Asian (EAS) AF: 0.419 AC: 2154 AN: 5140

South Asian (SAS) AF: 0.501 AC: 2407 AN: 4802

European-Finnish (FIN) AF: 0.480 AC: 5062 AN: 10536

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.433 AC: 29432 AN: 67938

Other (OTH) AF: 0.361 AC: 759 AN: 2100

Alfa AF: 0.398 Hom.: 6272

Bravo AF: 0.363

Asia WGS AF: 0.476 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.11
DANN	Benign	0.37
PhyloP100		-0.67
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: rs217290; hg19: chr6-84398565;