chr14-24912171-G-A

Variant names:

• chr14-24912171-G-A
• rs12885474
• NM_001394410.1:c.155-55014C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394410.1(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 NM_001394410.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394410.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP6	NM_001394410.1	MANE Select	c.155-55014C>T		intron	N/A	NP_001381339.1
	STXBP6	NM_001304476.3		c.155-55014C>T		intron	N/A	NP_001291405.1
	STXBP6	NM_001304477.3		c.155-55014C>T		intron	N/A	NP_001291406.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP6	ENST00000323944.10	TSL:1 MANE Select	c.155-55014C>T		intron	N/A	ENSP00000324302.5
	STXBP6	ENST00000396700.5	TSL:1	c.155-55014C>T		intron	N/A	ENSP00000379928.1
	STXBP6	ENST00000419632.6	TSL:1	c.155-55014C>T		intron	N/A	ENSP00000397212.2

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

African (AFR) AF: 0.176 AC: 7282 AN: 41434

American (AMR) AF: 0.0923 AC: 1409 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 303 AN: 3470

East Asian (EAS) AF: 0.168 AC: 866 AN: 5166

South Asian (SAS) AF: 0.147 AC: 710 AN: 4824

European-Finnish (FIN) AF: 0.170 AC: 1797 AN: 10582

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8229 AN: 67984

Other (OTH) AF: 0.123 AC: 259 AN: 2104

Alfa AF: 0.147 Hom.: 6712

Bravo AF: 0.136

Asia WGS AF: 0.173 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.26
PhyloP100		0.0030
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12885474; hg19: chr14-25381377;