Variant chr19-7647275-C-T 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.1538+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,610,808 control chromosomes in the GnomAD database, including 14,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.098 ( 970 hom., cov: 34)

Exomes 𝑓: 0.13 ( 13403 hom. )

Consequence

STXBP2
NM_006949.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.42

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:

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=-0.88).

BP6

Variant 19-7647275-C-T is Benign according to our data. Variant chr19-7647275-C-T is described in ClinVar as [Benign]. Clinvar id is 260092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 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.1538+28C>T		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.1538+28C>T		intron_variant		1	NM_006949.4	ENSP00000221283.4		Q15833-1
ENSG00000268400	ENST00000698368.1 linkuse as main transcript	n.*1641+28C>T		intron_variant				ENSP00000513686.1		A0A8V8TM65

Frequencies

GnomAD3 genomes

AF:

0.0983

AC:

14957

AN:

152136

Hom.:

970

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0979

Gnomad ASJ

AF:

0.0931

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0412

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.112

GnomAD3 exomes

AF:

0.103

AC:

24254

AN:

236208

Hom.:

1616

AF XY:

0.103

AC XY:

13364

AN XY:

129932

show subpopulations

Gnomad AFR exome

AF:

0.0248

Gnomad AMR exome

AF:

0.0861

Gnomad ASJ exome

AF:

0.0897

Gnomad EAS exome

AF:

0.000680

Gnomad SAS exome

AF:

0.0412

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.129

AC:

188743

AN:

1458554

Hom.:

13403

Cov.:

AF XY:

0.127

AC XY:

92347

AN XY:

725650

show subpopulations

Gnomad4 AFR exome

AF:

0.0210

Gnomad4 AMR exome

AF:

0.0874

Gnomad4 ASJ exome

AF:

0.0919

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0420

Gnomad4 FIN exome

AF:

0.149

Gnomad4 NFE exome

AF:

0.147

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.0982

AC:

14956

AN:

152254

Hom.:

970

Cov.:

AF XY:

0.0978

AC XY:

7279

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0253

Gnomad4 AMR

AF:

0.0977

Gnomad4 ASJ

AF:

0.0931

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0422

Gnomad4 FIN

AF:

0.148

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.118

Hom.:

229

Bravo

AF:

0.0937

Asia WGS

AF:

0.0350

AC:

122

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	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 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. 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	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.53

DANN

Benign

0.82

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.

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