rs12885474

Positions:

• chr14-24912171-G-A

Variant summary

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

The ENST00000323944.10(STXBP6):​c.155-55014C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,036 control chromosomes in the GnomAD database, including 1,533 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 0.14 (1533 hom., cov: 31)
• Consequence: STXBP6 ENST00000323944.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP6	NM_001394410.1	c.155-55014C>T		intron_variant		ENST00000323944.10	NP_001381339.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP6	ENST00000323944.10	c.155-55014C>T		intron_variant		1	NM_001394410.1	ENSP00000324302	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20961 AN: 151918 Hom.: 1527 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0925

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.138 AC: 21000 AN: 152036 Hom.: 1533 Cov.: 31 AF XY: 0.138 AC XY: 10285 AN XY: 74296

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0923

Gnomad4 ASJ AF: 0.0873

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.123

Alfa AF: 0.153 Hom.: 5523

Bravo AF: 0.136

Asia WGS AF: 0.173 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.26

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: rs12885474; hg19: chr14-25381377;