NM_003165.6:c.38-16_38-15delCT

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_003165.6(STXBP1):c.38-16_38-15delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,217,174 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 31)

Exomes 𝑓: 0.012 ( 0 hom. )

Consequence

STXBP1
NM_003165.6 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0900

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 4
Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
atypical Rett syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Dravet syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autism spectrum disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

STXBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP6

Variant 9-127651572-CCT-C is Benign according to our data. Variant chr9-127651572-CCT-C is described in ClinVar as [Benign]. Clinvar id is 207401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP1	NM_003165.6 link	c.38-16_38-15delCT		intron_variant	Intron 1 of 19	ENST00000373302.8	NP_003156.1	P61764-2
STXBP1	NM_001032221.6 link	c.38-16_38-15delCT		intron_variant	Intron 1 of 18	ENST00000373299.5	NP_001027392.1	P61764-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP1	ENST00000373302.8 link	c.38-30_38-29delCT		intron_variant	Intron 1 of 19	1	NM_003165.6	ENSP00000362399.3		P61764-2
STXBP1	ENST00000373299.5 link	c.38-30_38-29delCT		intron_variant	Intron 1 of 18	1	NM_001032221.6	ENSP00000362396.2		P61764-1

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

150408

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000976

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000930

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00206

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00290

GnomAD2 exomes

AF:

0.00823

AC:

1097

AN:

133350

AF XY:

0.00873

show subpopulations

Gnomad AFR exome

AF:

0.00615

Gnomad AMR exome

AF:

0.00730

Gnomad ASJ exome

AF:

0.00434

Gnomad EAS exome

AF:

0.00651

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.00831

Gnomad OTH exome

AF:

0.00823

GnomAD4 exome

AF:

0.0119

AC:

12704

AN:

1066654

Hom.:

AF XY:

0.0114

AC XY:

5991

AN XY:

525876

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0121

AC:

298

AN:

24616

American (AMR)

AF:

0.00832

AC:

268

AN:

32224

Ashkenazi Jewish (ASJ)

AF:

0.0128

AC:

228

AN:

17854

East Asian (EAS)

AF:

0.0113

AC:

312

AN:

27520

South Asian (SAS)

AF:

0.00667

AC:

371

AN:

55652

European-Finnish (FIN)

AF:

0.0123

AC:

488

AN:

39730

Middle Eastern (MID)

AF:

0.0110

AC:

AN:

4566

European-Non Finnish (NFE)

AF:

0.0123

AC:

10139

AN:

821040

Other (OTH)

AF:

0.0127

AC:

550

AN:

43452

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.243

Heterozygous variant carriers

2145

4291

6436

8582

10727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000598

AC:

AN:

150520

Hom.:

Cov.:

AF XY:

0.000667

AC XY:

AN XY:

73480

show subpopulations

African (AFR)

AF:

0.000973

AC:

AN:

41116

American (AMR)

AF:

0.000929

AC:

AN:

15066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4758

European-Finnish (FIN)

AF:

0.00206

AC:

AN:

10190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000133

AC:

AN:

67512

Other (OTH)

AF:

0.00287

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0687

Hom.:

Bravo

AF:

0.000472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 19, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The variant is found in EPILEPSY,INFANT-EPI panel(s). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.090

Mutation Taster

=100/0

polymorphism

(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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NM_003165.6:c.38-16_38-15delCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over