17-54984261-T-C

Variant names:

• chr17-54984261-T-C
• rs9902718
• NM_178509.6:c.-156-1353T>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.-156-1353T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,402 control chromosomes in the GnomAD database, including 6,173 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 0.28 (6173 hom., cov: 30)
• Consequence: STXBP4 NM_178509.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 10 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 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.-156-1353T>C		intron	N/A	NP_848604.3
	STXBP4	NM_001398481.1		c.-156-1353T>C		intron	N/A	NP_001385410.1
	STXBP4	NM_001398483.1		c.-156-1353T>C		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.-156-1353T>C		intron	N/A	ENSP00000365530.2
	STXBP4	ENST00000434978.6	TSL:1	c.-156-1353T>C		intron	N/A	ENSP00000391087.2
	STXBP4	ENST00000398391.6	TSL:1	c.-254-1353T>C		intron	N/A	ENSP00000381427.2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42246 AN: 151288 Hom.: 6175 Cov.: 30

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0918

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.279 AC: 42257 AN: 151402 Hom.: 6173 Cov.: 30 AF XY: 0.275 AC XY: 20360 AN XY: 73926

African (AFR) AF: 0.350 AC: 14403 AN: 41184

American (AMR) AF: 0.228 AC: 3463 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 808 AN: 3470

East Asian (EAS) AF: 0.0912 AC: 472 AN: 5174

South Asian (SAS) AF: 0.168 AC: 805 AN: 4802

European-Finnish (FIN) AF: 0.267 AC: 2770 AN: 10356

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18730 AN: 67912

Other (OTH) AF: 0.290 AC: 611 AN: 2104

Alfa AF: 0.273 Hom.: 2706

Bravo AF: 0.282

Asia WGS AF: 0.152 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.35
PhyloP100		-0.38
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: rs9902718; hg19: chr17-53061622;