rs17257773

Positions:

• chr14-25041878-G-C

Variant summary

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

The NM_001394410.1(STXBP6):​c.-33+8000C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 152,180 control chromosomes in the GnomAD database, including 455 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 0.069 (455 hom., cov: 33)
• Consequence: STXBP6 NM_001394410.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519

Genes affected

STXBP6 (HGNC:19666): (syntaxin binding protein 6) Enables cadherin binding activity involved in cell-cell adhesion. Predicted to be involved in Golgi to plasma membrane transport and exocytosis. Located in adherens junction. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP6	NM_001394410.1	c.-33+8000C>G		intron_variant		ENST00000323944.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP6	ENST00000323944.10	c.-33+8000C>G		intron_variant		1	NM_001394410.1	P1

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10509 AN: 152062 Hom.: 446 Cov.: 33

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0819

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0719

Gnomad OTH AF: 0.0696

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

GnomAD4 genome AF: 0.0693 AC: 10552 AN: 152180 Hom.: 455 Cov.: 33 AF XY: 0.0724 AC XY: 5384 AN XY: 74378

Gnomad4 AFR AF: 0.0374

Gnomad4 AMR AF: 0.0826

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0922

Gnomad4 NFE AF: 0.0719

Gnomad4 OTH AF: 0.0736

Alfa AF: 0.0689 Hom.: 47

Bravo AF: 0.0668

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.60

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: rs17257773; hg19: chr14-25511084;