19-7645324-A-G

Variant summary

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

The NM_006949.4(STXBP2):​c.1356+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,563,216 control chromosomes in the GnomAD database, including 124,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15738 hom., cov: 34)
Exomes 𝑓: 0.39 ( 108677 hom. )

Consequence

STXBP2
NM_006949.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.379
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]

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 19-7645324-A-G is Benign according to our data. Variant chr19-7645324-A-G is described in ClinVar as [Benign]. Clinvar id is 260088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-7645324-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STXBP2NM_006949.4 linkc.1356+18A>G intron_variant Intron 15 of 18 ENST00000221283.10 NP_008880.2 Q15833-1Q53GF4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STXBP2ENST00000221283.10 linkc.1356+18A>G intron_variant Intron 15 of 18 1 NM_006949.4 ENSP00000221283.4 Q15833-1
ENSG00000268400ENST00000698368.1 linkn.*1459+18A>G intron_variant Intron 17 of 19 ENSP00000513686.1 A0A8V8TM65

Frequencies

GnomAD3 genomes
AF:
0.445
AC:
67619
AN:
152006
Hom.:
15704
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.538
Gnomad AMI
AF:
0.209
Gnomad AMR
AF:
0.470
Gnomad ASJ
AF:
0.311
Gnomad EAS
AF:
0.703
Gnomad SAS
AF:
0.362
Gnomad FIN
AF:
0.526
Gnomad MID
AF:
0.345
Gnomad NFE
AF:
0.367
Gnomad OTH
AF:
0.426
GnomAD3 exomes
AF:
0.423
AC:
74270
AN:
175436
Hom.:
16419
AF XY:
0.415
AC XY:
38790
AN XY:
93478
show subpopulations
Gnomad AFR exome
AF:
0.545
Gnomad AMR exome
AF:
0.457
Gnomad ASJ exome
AF:
0.304
Gnomad EAS exome
AF:
0.678
Gnomad SAS exome
AF:
0.346
Gnomad FIN exome
AF:
0.511
Gnomad NFE exome
AF:
0.368
Gnomad OTH exome
AF:
0.400
GnomAD4 exome
AF:
0.386
AC:
544019
AN:
1411092
Hom.:
108677
Cov.:
32
AF XY:
0.384
AC XY:
267644
AN XY:
697502
show subpopulations
Gnomad4 AFR exome
AF:
0.548
Gnomad4 AMR exome
AF:
0.459
Gnomad4 ASJ exome
AF:
0.307
Gnomad4 EAS exome
AF:
0.722
Gnomad4 SAS exome
AF:
0.343
Gnomad4 FIN exome
AF:
0.503
Gnomad4 NFE exome
AF:
0.366
Gnomad4 OTH exome
AF:
0.401
GnomAD4 genome
AF:
0.445
AC:
67710
AN:
152124
Hom.:
15738
Cov.:
34
AF XY:
0.451
AC XY:
33564
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.538
Gnomad4 AMR
AF:
0.470
Gnomad4 ASJ
AF:
0.311
Gnomad4 EAS
AF:
0.703
Gnomad4 SAS
AF:
0.362
Gnomad4 FIN
AF:
0.526
Gnomad4 NFE
AF:
0.367
Gnomad4 OTH
AF:
0.430
Alfa
AF:
0.390
Hom.:
2192
Bravo
AF:
0.447
Asia WGS
AF:
0.533
AC:
1851
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Mar 08, 2018
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Nov 12, 2023
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 70% of patients studied by a panel of primary immunodeficiencies. Number of patients: 67. Only high quality variants are reported. -

-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Familial hemophagocytic lymphohistiocytosis 5 Benign:2
Jul 15, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Feb 04, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Nov 12, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.60
DANN
Benign
0.21
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.

Other links and lift over

dbSNP: rs889187; hg19: chr19-7710210; COSMIC: COSV55405675; COSMIC: COSV55405675; API