Variant rs809916 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.12

Variant links:

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]

STXBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
STXBP2	NM_006949.4 linkuse as main transcript	c.1539-47G>A		intron_variant		ENST00000221283.10	NP_008880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP2	ENST00000221283.10 linkuse as main transcript	c.1539-47G>A		intron_variant		1	NM_006949.4	ENSP00000221283	P4	Q15833-1

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32481

AN:

152084

Hom.:

3594

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.235

AC XY:

170723

AN XY:

726110

show subpopulations

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.:

AF XY:

0.210

AC XY:

15654

AN XY:

74410

show subpopulations

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over