rs138763389

Positions:

chr9-127651600-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001032221.6(STXBP1):c.38-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,613,388 control chromosomes in the GnomAD database, including 392 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 27 hom., cov: 31)

Exomes 𝑓: 0.019 ( 365 hom. )

Consequence

STXBP1
NM_001032221.6 splice_region, intron

Scores

Splicing: ADA: 0.00004480

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.85

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:

STXBP1 (HGNC:):

STXBP1 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=-0.49).

BP6

Variant 9-127651600-T-C is Benign according to our data. Variant chr9-127651600-T-C is described in ClinVar as [Benign]. Clinvar id is 139343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-127651600-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0127 (1935/152170) while in subpopulation NFE AF= 0.0185 (1257/68008). AF 95% confidence interval is 0.0176. There are 27 homozygotes in gnomad4. There are 954 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1935 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP1	NM_003165.6 linkuse as main transcript	c.38-3T>C		splice_region_variant, intron_variant		ENST00000373302.8	NP_003156.1	P61764-2
STXBP1	NM_001032221.6 linkuse as main transcript	c.38-3T>C		splice_region_variant, 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.38-3T>C		splice_region_variant, intron_variant		1	NM_003165.6	ENSP00000362399.3		P61764-2
STXBP1	ENST00000373299.5 linkuse as main transcript	c.38-3T>C		splice_region_variant, intron_variant		1	NM_001032221.6	ENSP00000362396.2		P61764-1

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1935

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00411

Gnomad AMI

AF:

0.0495

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0185

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.0119

AC:

2997

AN:

251178

Hom.:

AF XY:

0.0116

AC XY:

1569

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.00357

Gnomad AMR exome

AF:

0.00451

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.0302

Gnomad NFE exome

AF:

0.0169

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0193

AC:

28141

AN:

1461218

Hom.:

365

Cov.:

AF XY:

0.0184

AC XY:

13399

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.00317

Gnomad4 AMR exome

AF:

0.00434

Gnomad4 ASJ exome

AF:

0.0111

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000615

Gnomad4 FIN exome

AF:

0.0284

Gnomad4 NFE exome

AF:

0.0222

Gnomad4 OTH exome

AF:

0.0209

GnomAD4 genome

AF:

0.0127

AC:

1935

AN:

152170

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

954

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00410

Gnomad4 AMR

AF:

0.00602

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0292

Gnomad4 NFE

AF:

0.0185

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.0145

Hom.:

Bravo

AF:

0.0116

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0182

EpiControl

AF:

0.0167

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 30, 2012	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 28, 2017	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 25, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.9

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000045

dbscSNV1_RF

Benign

0.0

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