Genetic Variant STXBP5:p.Leu815Leu (chr6-147359223-A-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7BA1

The NM_001127715.4(STXBP5):c.2445A>G(p.Leu815Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,613,772 control chromosomes in the GnomAD database, including 251,496 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 23202 hom., cov: 32)

Exomes 𝑓: 0.56 ( 228294 hom. )

Consequence

STXBP5
NM_001127715.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0930

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP7

Synonymous conserved (PhyloP=-0.093 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP5	NM_001127715.4 link	c.2445A>G	p.Leu815Leu	synonymous_variant	Exon 23 of 28	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.2445A>G	p.Leu815Leu	synonymous_variant	Exon 23 of 28	5	NM_001127715.4	ENSP00000321826.6		Q5T5C0-1

Frequencies

GnomAD3 genomes

AF:

0.550

AC:

83514

AN:

151938

Hom.:

23192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.580

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.559

Gnomad ASJ

AF:

0.555

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.525

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.559

Gnomad OTH

AF:

0.558

GnomAD2 exomes

AF:

0.530

AC:

133264

AN:

251250

AF XY:

0.531

show subpopulations

Gnomad AFR exome

AF:

0.570

Gnomad AMR exome

AF:

0.556

Gnomad ASJ exome

AF:

0.554

Gnomad EAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.504

Gnomad NFE exome

AF:

0.561

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.556

AC:

813023

AN:

1461716

Hom.:

228294

Cov.:

AF XY:

0.555

AC XY:

403582

AN XY:

727170

show subpopulations

African (AFR)

AF:

0.582

AC:

19467

AN:

33466

American (AMR)

AF:

0.554

AC:

24750

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

14544

AN:

26132

East Asian (EAS)

AF:

0.274

AC:

10888

AN:

39694

South Asian (SAS)

AF:

0.532

AC:

45930

AN:

86254

European-Finnish (FIN)

AF:

0.511

AC:

27320

AN:

53418

Middle Eastern (MID)

AF:

0.579

AC:

3337

AN:

5764

European-Non Finnish (NFE)

AF:

0.570

AC:

633999

AN:

1111900

Other (OTH)

AF:

0.543

AC:

32788

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

21753

43507

65260

87014

108767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.550

AC:

83566

AN:

152056

Hom.:

23202

Cov.:

AF XY:

0.544

AC XY:

40430

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.580

AC:

24056

AN:

41488

American (AMR)

AF:

0.560

AC:

8545

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.555

AC:

1925

AN:

3466

East Asian (EAS)

AF:

0.275

AC:

1418

AN:

5150

South Asian (SAS)

AF:

0.524

AC:

2527

AN:

4820

European-Finnish (FIN)

AF:

0.505

AC:

5327

AN:

10556

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.559

AC:

37982

AN:

67992

Other (OTH)

AF:

0.555

AC:

1170

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1967

3935

5902

7870

9837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.556

Hom.:

110538

Bravo

AF:

0.555

Asia WGS

AF:

0.432

AC:

1501

AN:

3478

EpiCase

AF:

0.567

EpiControl

AF:

0.574

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.3

(source)

DANN

Benign

0.40

PhyloP100

-0.093

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=99/1

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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chr6-147359223-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over