Genetic Variant STXBP5:c.1361+80C>T (chr6-147314411-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001127715.4(STXBP5):c.1361+80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,392,420 control chromosomes in the GnomAD database, including 232,782 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 24777 hom., cov: 31)

Exomes 𝑓: 0.58 ( 208005 hom. )

Consequence

STXBP5
NM_001127715.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.46

Publications

6 publications found

Variant links:

Genes affected

STXBP5 (HGNC:19665): (syntaxin binding protein 5) Syntaxin 1 is a component of the 7S and 20S SNARE complexes which are involved in docking and fusion of synaptic vesicles with the presynaptic plasma membrane. This gene encodes a syntaxin 1 binding protein. In rat, a similar protein dissociates syntaxin 1 from the Munc18/n-Sec1/rbSec1 complex to form a 10S complex, an intermediate which can be converted to the 7S SNARE complex. Thus this protein is thought to be involved in neurotransmitter release by stimulating SNARE complex formation. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

STXBP5 links:

ENSG00000293909 (HGNC:):

ENSG00000293909 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP5	NM_001127715.4 link	c.1361+80C>T		intron_variant	Intron 13 of 27	ENST00000321680.11	NP_001121187.1	Q5T5C0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP5	ENST00000321680.11 link	c.1361+80C>T		intron_variant	Intron 13 of 27	5	NM_001127715.4	ENSP00000321826.6		Q5T5C0-1

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

86227

AN:

151778

Hom.:

24777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.564

Gnomad AMI

AF:

0.482

Gnomad AMR

AF:

0.600

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.539

Gnomad FIN

AF:

0.535

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.594

Gnomad OTH

AF:

0.557

GnomAD4 exome

AF:

0.576

AC:

714607

AN:

1240524

Hom.:

208005

Cov.:

AF XY:

0.576

AC XY:

360717

AN XY:

626762

show subpopulations

African (AFR)

AF:

0.556

AC:

16126

AN:

29002

American (AMR)

AF:

0.606

AC:

25849

AN:

42646

Ashkenazi Jewish (ASJ)

AF:

0.554

AC:

13623

AN:

24590

East Asian (EAS)

AF:

0.293

AC:

11247

AN:

38396

South Asian (SAS)

AF:

0.545

AC:

44262

AN:

81212

European-Finnish (FIN)

AF:

0.541

AC:

28206

AN:

52166

Middle Eastern (MID)

AF:

0.560

AC:

2730

AN:

4872

European-Non Finnish (NFE)

AF:

0.593

AC:

542904

AN:

914872

Other (OTH)

AF:

0.562

AC:

29660

AN:

52768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

13777

27555

41332

55110

68887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13728

27456

41184

54912

68640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.568

AC:

86275

AN:

151896

Hom.:

24777

Cov.:

AF XY:

0.563

AC XY:

41757

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.564

AC:

23369

AN:

41446

American (AMR)

AF:

0.600

AC:

9146

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.551

AC:

1912

AN:

3470

East Asian (EAS)

AF:

0.291

AC:

1505

AN:

5166

South Asian (SAS)

AF:

0.538

AC:

2595

AN:

4824

European-Finnish (FIN)

AF:

0.535

AC:

5638

AN:

10532

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.594

AC:

40326

AN:

67908

Other (OTH)

AF:

0.554

AC:

1165

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1864

3729

5593

7458

9322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.587

Hom.:

33396

Bravo

AF:

0.572

Asia WGS

AF:

0.452

AC:

1570

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.20

(source)

DANN

Benign

0.32

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over