rs755101

Variant names:

• chr6-83678457-T-C
• rs755101
• NM_001242792.2:c.131-12876A>G

Variant summary

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

The NM_001242792.2(SNAP91):​c.131-12876A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,066 control chromosomes in the GnomAD database, including 4,289 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 0.21 (4289 hom., cov: 32)
• Consequence: SNAP91 NM_001242792.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP91	NM_001242792.2	c.131-12876A>G		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.131-12876A>G		intron_variant	Intron 2 of 29	5	NM_001242792.2	ENSP00000358708.2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32433 AN: 151948 Hom.: 4279 Cov.: 32

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.213 AC: 32450 AN: 152066 Hom.: 4289 Cov.: 32 AF XY: 0.217 AC XY: 16144 AN XY: 74328

African (AFR) AF: 0.0608 AC: 2525 AN: 41516

American (AMR) AF: 0.305 AC: 4651 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3468

East Asian (EAS) AF: 0.399 AC: 2057 AN: 5158

South Asian (SAS) AF: 0.303 AC: 1461 AN: 4826

European-Finnish (FIN) AF: 0.245 AC: 2591 AN: 10560

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17333 AN: 67962

Other (OTH) AF: 0.234 AC: 494 AN: 2112

Alfa AF: 0.225 Hom.: 625

Bravo AF: 0.213

Asia WGS AF: 0.274 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.066
DANN	Benign	0.50
PhyloP100		-1.1
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: rs755101; hg19: chr6-84388176;