rs809916

chr19-7647307-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006949.4(STXBP2):c.1539-47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,611,754 control chromosomes in the GnomAD database, including 45,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3599 hom., cov: 33)
  • Exomes 𝑓: 0.24 (42282 hom.)
• Consequence: STXBP2 NM_006949.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.12

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-7647307-G-A is Benign according to our data. Variant chr19-7647307-G-A is described in ClinVar as [Benign]. Clinvar id is 260093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP2	NM_006949.4	c.1539-47G>A		intron_variant		ENST00000221283.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP2	ENST00000221283.10	c.1539-47G>A		intron_variant		1	NM_006949.4	P4

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32481 AN: 152084 Hom.: 3594 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.210

GnomAD3 exomes AF: 0.208 AC: 49872 AN: 239806 Hom.: 5417 AF XY: 0.207 AC XY: 27201 AN XY: 131434

Gnomad AFR exome AF: 0.184

Gnomad AMR exome AF: 0.189

Gnomad ASJ exome AF: 0.205

Gnomad EAS exome AF: 0.126

Gnomad SAS exome AF: 0.148

Gnomad FIN exome AF: 0.216

Gnomad NFE exome AF: 0.246

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.238 AC: 346814 AN: 1459552 Hom.: 42282 Cov.: 56 AF XY: 0.235 AC XY: 170723 AN XY: 726110

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.214 AC: 32501 AN: 152202 Hom.: 3599 Cov.: 33 AF XY: 0.210 AC XY: 15654 AN XY: 74410

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.210

Alfa AF: 0.223 Hom.: 730

Bravo AF: 0.216

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 41% of patients studied by a panel of primary immunodeficiencies. Number of patients: 39. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.51
Dann	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs809916; hg19: chr19-7712193;