rs217289

Variant names:

• chr6-83692088-G-A
• rs217289
• NM_001242792.2:c.130+15710C>T

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+15710C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,896 control chromosomes in the GnomAD database, including 10,913 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 0.36 (10913 hom., cov: 32)
• Consequence: SNAP91 NM_001242792.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP91	NM_001242792.2	c.130+15710C>T		intron_variant	Intron 2 of 29	ENST00000369694.7	NP_001229721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP91	ENST00000369694.7	c.130+15710C>T		intron_variant	Intron 2 of 29	5	NM_001242792.2	ENSP00000358708.2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55174 AN: 151778 Hom.: 10907 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.363 AC: 55198 AN: 151896 Hom.: 10913 Cov.: 32 AF XY: 0.367 AC XY: 27221 AN XY: 74228

African (AFR) AF: 0.199 AC: 8260 AN: 41414

American (AMR) AF: 0.364 AC: 5553 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3470

East Asian (EAS) AF: 0.422 AC: 2175 AN: 5160

South Asian (SAS) AF: 0.500 AC: 2409 AN: 4816

European-Finnish (FIN) AF: 0.480 AC: 5057 AN: 10526

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29448 AN: 67934

Other (OTH) AF: 0.346 AC: 728 AN: 2106

Alfa AF: 0.386 Hom.: 1965

Bravo AF: 0.344

Asia WGS AF: 0.473 AC: 1643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.70
DANN	Benign	0.17
PhyloP100		-0.37
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: rs217289; hg19: chr6-84401807;