Variant 19-7647539-G-C 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.1696+28G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,573,874 control chromosomes in the GnomAD database, including 96,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9250 hom., cov: 31)

Exomes 𝑓: 0.35 ( 86779 hom. )

Consequence

STXBP2
NM_006949.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.63

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 19-7647539-G-C is Benign according to our data. Variant chr19-7647539-G-C is described in ClinVar as [Benign]. Clinvar id is 260100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP2	NM_006949.4 link	c.1696+28G>C		intron_variant		ENST00000221283.10	NP_008880.2	Q15833-1Q53GF4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP2	ENST00000221283.10 link	c.1696+28G>C		intron_variant		1	NM_006949.4	ENSP00000221283.4		Q15833-1

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52567

AN:

151830

Hom.:

9232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.364

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.351

GnomAD3 exomes

AF:

0.336

AC:

64667

AN:

192400

Hom.:

10956

AF XY:

0.332

AC XY:

34622

AN XY:

104176

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.354

Gnomad ASJ exome

AF:

0.269

Gnomad EAS exome

AF:

0.212

Gnomad SAS exome

AF:

0.268

Gnomad FIN exome

AF:

0.444

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.355

GnomAD4 exome

AF:

0.348

AC:

494449

AN:

1421926

Hom.:

86779

Cov.:

AF XY:

0.345

AC XY:

243285

AN XY:

704192

show subpopulations

Gnomad4 AFR exome

AF:

0.334

Gnomad4 AMR exome

AF:

0.354

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.237

Gnomad4 SAS exome

AF:

0.271

Gnomad4 FIN exome

AF:

0.438

Gnomad4 NFE exome

AF:

0.356

Gnomad4 OTH exome

AF:

0.338

GnomAD4 genome

AF:

0.346

AC:

52615

AN:

151948

Hom.:

9250

Cov.:

AF XY:

0.348

AC XY:

25833

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.330

Gnomad4 AMR

AF:

0.364

Gnomad4 ASJ

AF:

0.274

Gnomad4 EAS

AF:

0.230

Gnomad4 SAS

AF:

0.269

Gnomad4 FIN

AF:

0.454

Gnomad4 NFE

AF:

0.355

Gnomad4 OTH

AF:

0.355

Alfa

AF:

0.235

Hom.:

776

Bravo

AF:

0.339

Asia WGS

AF:

0.282

AC:

983

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 46. Only high quality variants are reported. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Familial hemophagocytic lymphohistiocytosis 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.4

DANN

Benign

0.78

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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