Variant 19-7645154-T-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.1247-43T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,543,710 control chromosomes in the GnomAD database, including 125,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16859 hom., cov: 33)

Exomes 𝑓: 0.39 ( 108175 hom. )

Consequence

STXBP2
NM_006949.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.54

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=-0.92).

BP6

Variant 19-7645154-T-C is Benign according to our data. Variant chr19-7645154-T-C is described in ClinVar as [Benign]. Clinvar id is 260087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP2	NM_006949.4 linkuse as main transcript	c.1247-43T>C		intron_variant		ENST00000221283.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP2	ENST00000221283.10 linkuse as main transcript	c.1247-43T>C		intron_variant		1	NM_006949.4	P4	Q15833-1

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

69598

AN:

151950

Hom.:

16824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.584

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.704

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.527

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.367

Gnomad OTH

AF:

0.435

GnomAD3 exomes

AF:

0.424

AC:

65453

AN:

154326

Hom.:

14692

AF XY:

0.415

AC XY:

33873

AN XY:

81640

show subpopulations

Gnomad AFR exome

AF:

0.592

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.303

Gnomad EAS exome

AF:

0.677

Gnomad SAS exome

AF:

0.344

Gnomad FIN exome

AF:

0.509

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.401

GnomAD4 exome

AF:

0.387

AC:

538061

AN:

1391642

Hom.:

108175

Cov.:

AF XY:

0.385

AC XY:

264268

AN XY:

686858

show subpopulations

Gnomad4 AFR exome

AF:

0.598

Gnomad4 AMR exome

AF:

0.462

Gnomad4 ASJ exome

AF:

0.307

Gnomad4 EAS exome

AF:

0.724

Gnomad4 SAS exome

AF:

0.343

Gnomad4 FIN exome

AF:

0.502

Gnomad4 NFE exome

AF:

0.366

Gnomad4 OTH exome

AF:

0.403

GnomAD4 genome

AF:

0.458

AC:

69690

AN:

152068

Hom.:

16859

Cov.:

AF XY:

0.464

AC XY:

34492

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.584

Gnomad4 AMR

AF:

0.473

Gnomad4 ASJ

AF:

0.311

Gnomad4 EAS

AF:

0.703

Gnomad4 SAS

AF:

0.362

Gnomad4 FIN

AF:

0.527

Gnomad4 NFE

AF:

0.367

Gnomad4 OTH

AF:

0.439

Alfa

AF:

0.395

Hom.:

2264

Bravo

AF:

0.461

Asia WGS

AF:

0.533

AC:

1854

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 71% of patients studied by a panel of primary immunodeficiencies. Number of patients: 68. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Familial hemophagocytic lymphohistiocytosis 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

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

-0.92

Cadd

Benign

0.43

Dann

Benign

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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