rs11658717

Variant names:

• chr17-54999625-G-A
• rs11658717
• NM_178509.6:c.288-7G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-54999625-G-A
• chr17-54999625-G-C
• chr17-54999625-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 4P and 8B. PVS1_Strong BA1

The NM_001398481.1(STXBP4):​c.288-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 1,608,732 control chromosomes in the GnomAD database, including 423,129 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.72 (39303 hom., cov: 32)
  • Exomes 𝑓: 0.72 (383826 hom.)
• Consequence: STXBP4 NM_001398481.1 splice_acceptor, intron
• Scores: Splicing: ADA: 0.0003532
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

Genes affected

STXBP4 (HGNC:19694): (syntaxin binding protein 4) Enables syntaxin binding activity. Involved in several processes, including positive regulation of cell cycle G1/S phase transition; positive regulation of keratinocyte proliferation; and protein stabilization. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.13009593 fraction of the gene. Cryptic splice site detected, with MaxEntScore 7.3, offset of 6, new splice context is: tgatttctttttaatactAGgtt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP4	NM_178509.6	c.288-7G>A		splice_region_variant, intron_variant	Intron 5 of 17	ENST00000376352.6	NP_848604.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP4	ENST00000376352.6	c.288-7G>A		splice_region_variant, intron_variant	Intron 5 of 17	2	NM_178509.6	ENSP00000365530.2

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108872 AN: 151930 Hom.: 39256 Cov.: 32

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.699

GnomAD2 exomes AF: 0.757 AC: 187246 AN: 247348 AF XY: 0.757

Gnomad AFR exome AF: 0.652

Gnomad AMR exome AF: 0.843

Gnomad ASJ exome AF: 0.760

Gnomad EAS exome AF: 0.894

Gnomad FIN exome AF: 0.726

Gnomad NFE exome AF: 0.716

Gnomad OTH exome AF: 0.739

GnomAD4 exome AF: 0.724 AC: 1054201 AN: 1456684 Hom.: 383826 Cov.: 33 AF XY: 0.727 AC XY: 526723 AN XY: 724752

Gnomad4 AFR exome AF: 0.656 AC: 21773 AN: 33204

Gnomad4 AMR exome AF: 0.836 AC: 36998 AN: 44260

Gnomad4 ASJ exome AF: 0.761 AC: 19757 AN: 25962

Gnomad4 EAS exome AF: 0.928 AC: 36732 AN: 39566

Gnomad4 SAS exome AF: 0.811 AC: 69410 AN: 85576

Gnomad4 FIN exome AF: 0.723 AC: 38524 AN: 53314

Gnomad4 NFE exome AF: 0.706 AC: 783092 AN: 1108874

Gnomad4 Remaining exome AF: 0.725 AC: 43608 AN: 60182

GnomAD4 genome AF: 0.717 AC: 108983 AN: 152048 Hom.: 39303 Cov.: 32 AF XY: 0.721 AC XY: 53555 AN XY: 74308

Gnomad4 AFR AF: 0.661 AC: 0.660693 AN: 0.660693

Gnomad4 AMR AF: 0.766 AC: 0.76596 AN: 0.76596

Gnomad4 ASJ AF: 0.756 AC: 0.756048 AN: 0.756048

Gnomad4 EAS AF: 0.908 AC: 0.907879 AN: 0.907879

Gnomad4 SAS AF: 0.826 AC: 0.825581 AN: 0.825581

Gnomad4 FIN AF: 0.726 AC: 0.726145 AN: 0.726145

Gnomad4 NFE AF: 0.713 AC: 0.712717 AN: 0.712717

Gnomad4 OTH AF: 0.699 AC: 0.699337 AN: 0.699337

Alfa AF: 0.719 Hom.: 110272

Bravo AF: 0.716

TwinsUK AF: 0.719 AC: 2667

ALSPAC AF: 0.710 AC: 2738

ESP6500AA AF: 0.649 AC: 2858

ESP6500EA AF: 0.715 AC: 6148

ExAC AF: 0.754 AC: 91471

Asia WGS AF: 0.847 AC: 2942 AN: 3478

EpiCase AF: 0.711

EpiControl AF: 0.714

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.73
Eigen	Benign	0.11
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.0010	N
GERP RS		2.4
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00035
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: rs11658717; hg19: chr17-53076986;