chr17-54999625-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178509.6(STXBP4):​c.288-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 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_178509.6 splice_region, intron
• Scores: Splicing: ADA: 0.0003532
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 29 publications found

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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.868523).
• 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

African (AFR) AF: 0.656 AC: 21773 AN: 33204

American (AMR) AF: 0.836 AC: 36998 AN: 44260

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 19757 AN: 25962

East Asian (EAS) AF: 0.928 AC: 36732 AN: 39566

South Asian (SAS) AF: 0.811 AC: 69410 AN: 85576

European-Finnish (FIN) AF: 0.723 AC: 38524 AN: 53314

Middle Eastern (MID) AF: 0.750 AC: 4307 AN: 5746

European-Non Finnish (NFE) AF: 0.706 AC: 783092 AN: 1108874

Other (OTH) 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

African (AFR) AF: 0.661 AC: 27391 AN: 41458

American (AMR) AF: 0.766 AC: 11710 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2625 AN: 3472

East Asian (EAS) AF: 0.908 AC: 4701 AN: 5178

South Asian (SAS) AF: 0.826 AC: 3976 AN: 4816

European-Finnish (FIN) AF: 0.726 AC: 7671 AN: 10564

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48432 AN: 67954

Other (OTH) AF: 0.699 AC: 1477 AN: 2112

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
PhyloP100		1.2
GERP RS		2.4
PromoterAI		-0.0033	Neutral
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

Other links and lift over

dbSNP: rs11658717; hg19: chr17-53076986;