chr6-83573042-A-G

Variant names:

• chr6-83573042-A-G
• rs2023238
• NM_001242792.2:c.2442+1968T>C

Variant summary

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

The NM_001242792.2(SNAP91):​c.2442+1968T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,056 control chromosomes in the GnomAD database, including 38,191 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 0.71 (38191 hom., cov: 31)
• Consequence: SNAP91 NM_001242792.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 4 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP91	NM_001242792.2	c.2442+1968T>C		intron_variant	Intron 26 of 29	ENST00000369694.7	NP_001229721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP91	ENST00000369694.7	c.2442+1968T>C		intron_variant	Intron 26 of 29	5	NM_001242792.2	ENSP00000358708.2

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107108 AN: 151938 Hom.: 38149 Cov.: 31

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.705 AC: 107201 AN: 152056 Hom.: 38191 Cov.: 31 AF XY: 0.705 AC XY: 52381 AN XY: 74318

African (AFR) AF: 0.796 AC: 33007 AN: 41450

American (AMR) AF: 0.591 AC: 9032 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2185 AN: 3470

East Asian (EAS) AF: 0.632 AC: 3260 AN: 5156

South Asian (SAS) AF: 0.781 AC: 3771 AN: 4826

European-Finnish (FIN) AF: 0.701 AC: 7412 AN: 10568

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46404 AN: 67998

Other (OTH) AF: 0.665 AC: 1399 AN: 2104

Alfa AF: 0.673 Hom.: 57725

Bravo AF: 0.694

Asia WGS AF: 0.692 AC: 2407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.77
DANN	Benign	0.44
PhyloP100		-1.9
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: rs2023238; hg19: chr6-84282761;