rs10147992

Positions:

• chr14-25034593-A-G
• chr14-25034593-A-T

Variant summary

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

The NM_001394410.1(STXBP6):​c.-33+15285T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,976 control chromosomes in the GnomAD database, including 19,562 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 0.48 (19562 hom., cov: 31)
• Consequence: STXBP6 NM_001394410.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP6	NM_001394410.1	c.-33+15285T>C		intron_variant		ENST00000323944.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP6	ENST00000323944.10	c.-33+15285T>C		intron_variant		1	NM_001394410.1	P1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73426 AN: 151858 Hom.: 19524 Cov.: 31

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.484 AC: 73522 AN: 151976 Hom.: 19562 Cov.: 31 AF XY: 0.482 AC XY: 35815 AN XY: 74266

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.451

Alfa AF: 0.394 Hom.: 14332

Bravo AF: 0.490

Asia WGS AF: 0.515 AC: 1791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.082
DANN	Benign	0.68

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: rs10147992; hg19: chr14-25503799;