rs4804758

Positions:

• chr19-7634406-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001414484.1(STXBP2):​c.-60+3560A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,190 control chromosomes in the GnomAD database, including 7,164 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 0.29 (7164 hom., cov: 33)
• Consequence: STXBP2 NM_001414484.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

ENSG00000268400 (HGNC:):

STXBP2 (HGNC:11445): (syntaxin binding protein 2) This gene encodes a member of the STXBP/unc-18/SEC1 family. The encoded protein is involved in intracellular trafficking, control of SNARE (soluble NSF attachment protein receptor) complex assembly, and the release of cytotoxic granules by natural killer cells. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2013]

PCP2 (HGNC:30209): (Purkinje cell protein 2) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to act upstream of or within rhodopsin mediated signaling pathway. Predicted to be located in neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP2	NM_001414484.1	c.-60+3560A>G		intron_variant			NP_001401413.1
PCP2	XM_006722639.4	c.-60-1576T>C		intron_variant			XP_006722702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000268400	ENST00000698368.1	n.115-2409A>G		intron_variant				ENSP00000513686.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44365 AN: 152072 Hom.: 7156 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.292 AC: 44386 AN: 152190 Hom.: 7164 Cov.: 33 AF XY: 0.292 AC XY: 21717 AN XY: 74406

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.306

Alfa AF: 0.318 Hom.: 1402

Bravo AF: 0.272

Asia WGS AF: 0.249 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4804758; hg19: chr19-7699292;