chr9-127651572-CCTCT-C

Variant names:

• chr9-127651572-CCTCT-C
• rs755475986
• NM_003165.6:c.38-18_38-15delCTCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001032221.6(STXBP1):​c.38-18_38-15delCTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000692 in 1,518,070 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000072 (0 hom.)
• Consequence: STXBP1 NM_001032221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP1	ENST00000373302.8	c.38-30_38-27delCTCT		intron_variant	Intron 1 of 19	1	NM_003165.6	ENSP00000362399.3
STXBP1	ENST00000373299.5	c.38-30_38-27delCTCT		intron_variant	Intron 1 of 18	1	NM_001032221.6	ENSP00000362396.2

Frequencies

GnomAD3 genomes AF: 0.0000465 AC: 7 AN: 150628 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000974

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000592

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000750 AC: 10 AN: 133350 AF XY: 0.0000857

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000112

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000812

Gnomad NFE exome AF: 0.0000965

Gnomad OTH exome AF: 0.000317

GnomAD4 exome AF: 0.0000717 AC: 98 AN: 1367442 Hom.: 0 AF XY: 0.0000822 AC XY: 56 AN XY: 680994

African (AFR) AF: 0.00 AC: 0 AN: 31546

American (AMR) AF: 0.0000469 AC: 2 AN: 42606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24666

East Asian (EAS) AF: 0.00 AC: 0 AN: 37724

South Asian (SAS) AF: 0.00 AC: 0 AN: 81248

European-Finnish (FIN) AF: 0.0000591 AC: 3 AN: 50742

Middle Eastern (MID) AF: 0.000360 AC: 2 AN: 5558

European-Non Finnish (NFE) AF: 0.0000830 AC: 86 AN: 1036652

Other (OTH) AF: 0.0000882 AC: 5 AN: 56700

GnomAD4 genome AF: 0.0000465 AC: 7 AN: 150628 Hom.: 0 Cov.: 31 AF XY: 0.0000408 AC XY: 3 AN XY: 73472

African (AFR) AF: 0.00 AC: 0 AN: 41020

American (AMR) AF: 0.000133 AC: 2 AN: 15084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4762

European-Finnish (FIN) AF: 0.0000974 AC: 1 AN: 10270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000592 AC: 4 AN: 67592

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.0000363 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.090
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs755475986; hg19: chr9-130413851;