rs140247913

Positions:

• chr9-127665348-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001032221.6(STXBP1):​c.663+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,613,468 control chromosomes in the GnomAD database, including 252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (22 hom., cov: 32)
  • Exomes 𝑓: 0.014 (230 hom.)
• Consequence: STXBP1 NM_001032221.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.27

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 9-127665348-C-T is Benign according to our data. Variant chr9-127665348-C-T is described in ClinVar as [Benign]. Clinvar id is 139347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-127665348-C-T is described in Lovd as [Likely_benign]. Variant chr9-127665348-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0139 (2120/152258) while in subpopulation SAS AF= 0.0201 (97/4820). AF 95% confidence interval is 0.0169. There are 22 homozygotes in gnomad4. There are 1136 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2120 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP1	NM_003165.6	c.663+17C>T		intron_variant		ENST00000373302.8	NP_003156.1
STXBP1	NM_001032221.6	c.663+17C>T		intron_variant		ENST00000373299.5	NP_001027392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP1	ENST00000373302.8	c.663+17C>T		intron_variant		1	NM_003165.6	ENSP00000362399.3
STXBP1	ENST00000373299.5	c.663+17C>T		intron_variant		1	NM_001032221.6	ENSP00000362396.2

Frequencies

GnomAD3 genomes AF: 0.0139 AC: 2120 AN: 152140 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.00838

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00989

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.0166 AC: 4169 AN: 251398 Hom.: 66 AF XY: 0.0168 AC XY: 2288 AN XY: 135864

Gnomad AFR exome AF: 0.00910

Gnomad AMR exome AF: 0.00885

Gnomad ASJ exome AF: 0.0241

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0230

Gnomad FIN exome AF: 0.0417

Gnomad NFE exome AF: 0.0157

Gnomad OTH exome AF: 0.0127

GnomAD4 exome AF: 0.0141 AC: 20664 AN: 1461210 Hom.: 230 Cov.: 31 AF XY: 0.0145 AC XY: 10518 AN XY: 726958

Gnomad4 AFR exome AF: 0.00962

Gnomad4 AMR exome AF: 0.00883

Gnomad4 ASJ exome AF: 0.0236

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0220

Gnomad4 FIN exome AF: 0.0398

Gnomad4 NFE exome AF: 0.0130

Gnomad4 OTH exome AF: 0.0125

GnomAD4 genome AF: 0.0139 AC: 2120 AN: 152258 Hom.: 22 Cov.: 32 AF XY: 0.0153 AC XY: 1136 AN XY: 74452

Gnomad4 AFR AF: 0.00843

Gnomad4 AMR AF: 0.00988

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.0438

Gnomad4 NFE AF: 0.0137

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0165 Hom.: 2

Bravo AF: 0.0112

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 26, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Early infantile epileptic encephalopathy with suppression bursts Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.0
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs140247913; hg19: chr9-130427627;