17-55132021-G-C

Variant names:

• chr17-55132021-G-C
• rs2787487
• NM_178509.6:c.1490-9289G>C

Variant summary

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

The NM_178509.6(STXBP4):​c.1490-9289G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,044 control chromosomes in the GnomAD database, including 31,539 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 0.63 (31539 hom., cov: 33)
• Consequence: STXBP4 NM_178509.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41
• Publications: 6 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 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.1490-9289G>C		intron	N/A	NP_848604.3
	STXBP4	NM_001398481.1		c.1496-9289G>C		intron	N/A	NP_001385410.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP4	ENST00000376352.6	TSL:2 MANE Select	c.1490-9289G>C		intron	N/A	ENSP00000365530.2
	STXBP4	ENST00000434978.6	TSL:1	c.1424-9289G>C		intron	N/A	ENSP00000391087.2

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96439 AN: 151926 Hom.: 31512 Cov.: 33

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.635 AC: 96522 AN: 152044 Hom.: 31539 Cov.: 33 AF XY: 0.630 AC XY: 46829 AN XY: 74312

African (AFR) AF: 0.788 AC: 32699 AN: 41506

American (AMR) AF: 0.535 AC: 8168 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1577 AN: 3464

East Asian (EAS) AF: 0.438 AC: 2261 AN: 5160

South Asian (SAS) AF: 0.520 AC: 2509 AN: 4826

European-Finnish (FIN) AF: 0.620 AC: 6522 AN: 10524

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40835 AN: 67972

Other (OTH) AF: 0.607 AC: 1281 AN: 2110

Alfa AF: 0.626 Hom.: 3778

Bravo AF: 0.634

Asia WGS AF: 0.527 AC: 1835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.52
PhyloP100		-3.4
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: rs2787487; hg19: chr17-53209382;