rs7222197

Positions:

• chr17-54970138-G-A

Variant summary

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

The NM_178509.6(STXBP4):​c.-157+1323G>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 152,084 control chromosomes in the GnomAD database, including 6,254 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 (6254 hom., cov: 32)
• Consequence: STXBP4 NM_178509.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP4	NM_178509.6	c.-157+1323G>A		intron_variant		ENST00000376352.6	NP_848604.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP4	ENST00000376352.6	c.-157+1323G>A		intron_variant		2	NM_178509.6	ENSP00000365530	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42666 AN: 151966 Hom.: 6256 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0928

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.274

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: 42679 AN: 152084 Hom.: 6254 Cov.: 32 AF XY: 0.277 AC XY: 20620 AN XY: 74348

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.0922

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.292

Alfa AF: 0.267 Hom.: 3300

Bravo AF: 0.282

Asia WGS AF: 0.152 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.50

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: rs7222197; hg19: chr17-53047499;