17-55132021-G-C

Position:

• chr17-55132021-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP4	NM_178509.6	c.1490-9289G>C		intron_variant		ENST00000376352.6	NP_848604.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP4	ENST00000376352.6	c.1490-9289G>C		intron_variant		2	NM_178509.6	ENSP00000365530	P1
STXBP4	ENST00000434978.6	c.1424-9289G>C		intron_variant		1		ENSP00000391087

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

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.607

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.52

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: rs2787487; hg19: chr17-53209382;