rs10001

Positions:

chr19-7646335-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006949.4(STXBP2):c.1443T>C(p.Asp481Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,605,256 control chromosomes in the GnomAD database, including 125,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14749 hom., cov: 32)

Exomes 𝑓: 0.38 ( 111175 hom. )

Consequence

STXBP2
NM_006949.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.00

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 19-7646335-T-C is Benign according to our data. Variant chr19-7646335-T-C is described in ClinVar as [Benign]. Clinvar id is 260089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-7646335-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1 with no splicing effect.

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	Protein	UniProt
STXBP2	NM_006949.4 linkuse as main transcript	c.1443T>C	p.Asp481Asp	synonymous_variant	16/19	ENST00000221283.10	NP_008880.2	Q15833-1Q53GF4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STXBP2	ENST00000221283.10 linkuse as main transcript	c.1443T>C	p.Asp481Asp	synonymous_variant	16/19	1	NM_006949.4	ENSP00000221283.4	Q15833-1
ENSG00000268400	ENST00000698368.1 linkuse as main transcript	n.*1546T>C		non_coding_transcript_exon_variant	18/20			ENSP00000513686.1	A0A8V8TM65
ENSG00000268400	ENST00000698368.1 linkuse as main transcript	n.*1546T>C		3_prime_UTR_variant	18/20			ENSP00000513686.1	A0A8V8TM65

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65729

AN:

151924

Hom.:

14720

Cov.:

show subpopulations

Gnomad AFR

AF:

0.496

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.464

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.704

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.527

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.367

Gnomad OTH

AF:

0.414

GnomAD3 exomes

AF:

0.418

AC:

97048

AN:

232440

Hom.:

21061

AF XY:

0.408

AC XY:

51322

AN XY:

125864

show subpopulations

Gnomad AFR exome

AF:

0.499

Gnomad AMR exome

AF:

0.454

Gnomad ASJ exome

AF:

0.303

Gnomad EAS exome

AF:

0.683

Gnomad SAS exome

AF:

0.343

Gnomad FIN exome

AF:

0.509

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.401

GnomAD4 exome

AF:

0.385

AC:

558921

AN:

1453214

Hom.:

111175

Cov.:

AF XY:

0.383

AC XY:

276300

AN XY:

722094

show subpopulations

Gnomad4 AFR exome

AF:

0.504

Gnomad4 AMR exome

AF:

0.455

Gnomad4 ASJ exome

AF:

0.306

Gnomad4 EAS exome

AF:

0.720

Gnomad4 SAS exome

AF:

0.342

Gnomad4 FIN exome

AF:

0.502

Gnomad4 NFE exome

AF:

0.366

Gnomad4 OTH exome

AF:

0.397

GnomAD4 genome

AF:

0.433

AC:

65815

AN:

152042

Hom.:

14749

Cov.:

AF XY:

0.440

AC XY:

32696

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.496

Gnomad4 AMR

AF:

0.464

Gnomad4 ASJ

AF:

0.310

Gnomad4 EAS

AF:

0.703

Gnomad4 SAS

AF:

0.361

Gnomad4 FIN

AF:

0.527

Gnomad4 NFE

AF:

0.367

Gnomad4 OTH

AF:

0.418

Alfa

AF:

0.383

Hom.:

5285

Bravo

AF:

0.432

Asia WGS

AF:

0.529

AC:

1839

AN:

3478

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

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

-0.72

CADD

Benign

0.11

DANN

Benign

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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