rs1894936

Positions:

• chr17-55043494-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178509.6(STXBP4):​c.945+169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 885,634 control chromosomes in the GnomAD database, including 35,078 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4644 hom., cov: 32)
  • Exomes 𝑓: 0.28 (30434 hom.)
• Consequence: STXBP4 NM_178509.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP4	NM_178509.6	c.945+169A>G		intron_variant		ENST00000376352.6	NP_848604.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP4	ENST00000376352.6	c.945+169A>G		intron_variant		2	NM_178509.6	ENSP00000365530	P1
STXBP4	ENST00000398391.6	c.721-118A>G		intron_variant		1		ENSP00000381427
STXBP4	ENST00000434978.6	c.945+169A>G		intron_variant		1		ENSP00000391087
STXBP4	ENST00000405898.5	c.946-118A>G		intron_variant		5		ENSP00000385944

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35567 AN: 151968 Hom.: 4638 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.280 AC: 205366 AN: 733548 Hom.: 30434 Cov.: 10 AF XY: 0.280 AC XY: 104471 AN XY: 373522

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.234 AC: 35587 AN: 152086 Hom.: 4644 Cov.: 32 AF XY: 0.235 AC XY: 17479 AN XY: 74332

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.223

Alfa AF: 0.265 Hom.: 726

Bravo AF: 0.219

Asia WGS AF: 0.246 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.49
DANN	Benign	0.66

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: rs1894936; hg19: chr17-53120855; COSMIC: COSV54843359; COSMIC: COSV54843359;