rs6504950

Variant names:

• chr17-54979110-G-A
• rs6504950
• NM_178509.6:c.-156-6504G>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.-156-6504G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,966 control chromosomes in the GnomAD database, including 6,249 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 (6249 hom., cov: 32)
• Consequence: STXBP4 NM_178509.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 145 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 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.-156-6504G>A		intron	N/A	NP_848604.3
	STXBP4	NM_001398481.1		c.-156-6504G>A		intron	N/A	NP_001385410.1
	STXBP4	NM_001398483.1		c.-156-6504G>A		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.-156-6504G>A		intron	N/A	ENSP00000365530.2
	STXBP4	ENST00000434978.6	TSL:1	c.-156-6504G>A		intron	N/A	ENSP00000391087.2
	STXBP4	ENST00000398391.6	TSL:1	c.-254-6504G>A		intron	N/A	ENSP00000381427.2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42668 AN: 151848 Hom.: 6251 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0930

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.281 AC: 42681 AN: 151966 Hom.: 6249 Cov.: 32 AF XY: 0.278 AC XY: 20615 AN XY: 74284

African (AFR) AF: 0.352 AC: 14592 AN: 41448

American (AMR) AF: 0.230 AC: 3513 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 809 AN: 3472

East Asian (EAS) AF: 0.0924 AC: 478 AN: 5172

South Asian (SAS) AF: 0.168 AC: 811 AN: 4814

European-Finnish (FIN) AF: 0.275 AC: 2905 AN: 10552

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

European-Non Finnish (NFE) AF: 0.276 AC: 18763 AN: 67916

Other (OTH) AF: 0.292 AC: 615 AN: 2106

Alfa AF: 0.276 Hom.: 11363

Bravo AF: 0.282

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.10
DANN	Benign	0.45
PhyloP100		-1.1
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: rs6504950; hg19: chr17-53056471;