rs8104339

Positions:

chr19-7638719-C-T

Variant summary

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

The NM_006949.4(STXBP2):c.38-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,613,500 control chromosomes in the GnomAD database, including 129,930 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14545 hom., cov: 31)

Exomes 𝑓: 0.39 ( 115385 hom. )

Consequence

STXBP2
NM_006949.4 splice_region, intron

Scores

Splicing: ADA: 0.00009990

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 1.46

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:

ENSG00000268400 (HGNC:):

ENSG00000268400 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 19-7638719-C-T is Benign according to our data. Variant chr19-7638719-C-T is described in ClinVar as [Benign]. Clinvar id is 260104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-7638719-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 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.38-7C>T		splice_region_variant, 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 linkuse as main transcript	c.38-7C>T		splice_region_variant, intron_variant		1	NM_006949.4	ENSP00000221283.4		Q15833-1
ENSG00000268400	ENST00000698368.1 linkuse as main transcript	n.*141-7C>T		splice_region_variant, intron_variant				ENSP00000513686.1		A0A8V8TM65

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65227

AN:

151816

Hom.:

14524

Cov.:

show subpopulations

Gnomad AFR

AF:

0.508

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.282

Gnomad EAS

AF:

0.671

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.490

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.408

GnomAD3 exomes

AF:

0.400

AC:

100573

AN:

251382

Hom.:

21253

AF XY:

0.398

AC XY:

54032

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.514

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.654

Gnomad SAS exome

AF:

0.355

Gnomad FIN exome

AF:

0.483

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.391

GnomAD4 exome

AF:

0.392

AC:

572736

AN:

1461566

Hom.:

115385

Cov.:

AF XY:

0.390

AC XY:

283881

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.517

Gnomad4 AMR exome

AF:

0.307

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.691

Gnomad4 SAS exome

AF:

0.353

Gnomad4 FIN exome

AF:

0.474

Gnomad4 NFE exome

AF:

0.382

Gnomad4 OTH exome

AF:

0.398

GnomAD4 genome

AF:

0.430

AC:

65289

AN:

151934

Hom.:

14545

Cov.:

AF XY:

0.433

AC XY:

32164

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.508

Gnomad4 AMR

AF:

0.370

Gnomad4 ASJ

AF:

0.282

Gnomad4 EAS

AF:

0.670

Gnomad4 SAS

AF:

0.371

Gnomad4 FIN

AF:

0.490

Gnomad4 NFE

AF:

0.383

Gnomad4 OTH

AF:

0.411

Alfa

AF:

0.390

Hom.:

8453

Bravo

AF:

0.425

Asia WGS

AF:

0.501

AC:

1741

AN:

3478

EpiCase

AF:

0.385

EpiControl

AF:

0.371

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 49. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Familial hemophagocytic lymphohistiocytosis 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Familial hemophagocytic lymphohistiocytosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.018

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