17-55060613-A-G

Variant names:

• chr17-55060613-A-G
• rs9303363
• NM_178509.6:c.1012-12287A>G

Variant summary

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

The NM_178509.6(STXBP4):​c.1012-12287A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,086 control chromosomes in the GnomAD database, including 48,233 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 0.79 (48233 hom., cov: 31)
• Consequence: STXBP4 NM_178509.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444
• Publications: 8 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_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178509.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP4	NM_178509.6	MANE Select	c.1012-12287A>G		intron	N/A	NP_848604.3
	STXBP4	NM_001398481.1		c.1018-12287A>G		intron	N/A	NP_001385410.1
	STXBP4	NM_001398483.1		c.1012-12287A>G		intron	N/A	NP_001385412.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP4	ENST00000376352.6	TSL:2 MANE Select	c.1012-12287A>G		intron	N/A	ENSP00000365530.2
	STXBP4	ENST00000434978.6	TSL:1	c.946-12287A>G		intron	N/A	ENSP00000391087.2

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120202 AN: 151968 Hom.: 48172 Cov.: 31

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.759

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.791 AC: 120327 AN: 152086 Hom.: 48233 Cov.: 31 AF XY: 0.792 AC XY: 58842 AN XY: 74334

African (AFR) AF: 0.913 AC: 37948 AN: 41546

American (AMR) AF: 0.799 AC: 12190 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2640 AN: 3468

East Asian (EAS) AF: 0.908 AC: 4702 AN: 5180

South Asian (SAS) AF: 0.827 AC: 3986 AN: 4820

European-Finnish (FIN) AF: 0.725 AC: 7660 AN: 10560

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48588 AN: 67930

Other (OTH) AF: 0.759 AC: 1604 AN: 2114

Alfa AF: 0.727 Hom.: 30292

Bravo AF: 0.803

Asia WGS AF: 0.862 AC: 2994 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.76
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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: rs9303363; hg19: chr17-53137974;