Variant 9-127690513-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001032221.6(STXBP1):c.1703-262G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 539,606 control chromosomes in the GnomAD database, including 316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.029 ( 80 hom., cov: 32)

Exomes 𝑓: 0.032 ( 236 hom. )

Consequence

STXBP1
NM_001032221.6 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0980

Variant links:

Genes affected

STXBP1 (HGNC:11444): (syntaxin binding protein 1) This gene encodes a syntaxin-binding protein. The encoded protein appears to play a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. Mutations in this gene have been associated with infantile epileptic encephalopathy-4. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

STXBP1 links:

PTRH1 (HGNC:27039): (peptidyl-tRNA hydrolase 1 homolog) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PTRH1 links:

ENSG00000279571 (HGNC:):

ENSG00000279571 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-127690513-G-A is Benign according to our data. Variant chr9-127690513-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1190332.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0294 (4476/152306) while in subpopulation NFE AF= 0.0397 (2698/68032). AF 95% confidence interval is 0.0384. There are 80 homozygotes in gnomad4. There are 2166 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4476 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP1	NM_003165.6 linkuse as main transcript	c.*17-262G>A		intron_variant		ENST00000373302.8	NP_003156.1	P61764-2
STXBP1	NM_001032221.6 linkuse as main transcript	c.1703-262G>A		intron_variant		ENST00000373299.5	NP_001027392.1	P61764-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP1	ENST00000373302.8 linkuse as main transcript	c.*17-262G>A		intron_variant		1	NM_003165.6	ENSP00000362399.3		P61764-2
STXBP1	ENST00000373299.5 linkuse as main transcript	c.1703-262G>A		intron_variant		1	NM_001032221.6	ENSP00000362396.2		P61764-1

Frequencies

GnomAD3 genomes

AF:

0.0294

AC:

4476

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0364

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.0304

Gnomad FIN

AF:

0.0227

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0397

Gnomad OTH

AF:

0.0258

GnomAD4 exome

AF:

0.0317

AC:

12290

AN:

387300

Hom.:

236

Cov.:

AF XY:

0.0318

AC XY:

6531

AN XY:

205170

show subpopulations

Gnomad4 AFR exome

AF:

0.0130

Gnomad4 AMR exome

AF:

0.0305

Gnomad4 ASJ exome

AF:

0.0231

Gnomad4 EAS exome

AF:

0.00169

Gnomad4 SAS exome

AF:

0.0277

Gnomad4 FIN exome

AF:

0.0293

Gnomad4 NFE exome

AF:

0.0379

Gnomad4 OTH exome

AF:

0.0294

GnomAD4 genome

AF:

0.0294

AC:

4476

AN:

152306

Hom.:

Cov.:

AF XY:

0.0291

AC XY:

2166

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0143

Gnomad4 AMR

AF:

0.0365

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.00405

Gnomad4 SAS

AF:

0.0304

Gnomad4 FIN

AF:

0.0227

Gnomad4 NFE

AF:

0.0397

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0364

Hom.:

Bravo

AF:

0.0285

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.2

DANN

Benign

0.33

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