14-25010336-C-T

Variant names:

• chr14-25010336-C-T
• rs11850957
• NM_001394410.1:c.-32-35486G>A

Variant summary

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

The NM_001394410.1(STXBP6):​c.-32-35486G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,052 control chromosomes in the GnomAD database, including 8,116 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 0.29 (8116 hom., cov: 33)
• Consequence: STXBP6 NM_001394410.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 11 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=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP6	NM_001394410.1	c.-32-35486G>A		intron_variant	Intron 1 of 5	ENST00000323944.10	NP_001381339.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP6	ENST00000323944.10	c.-32-35486G>A		intron_variant	Intron 1 of 5	1	NM_001394410.1	ENSP00000324302.5

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44283 AN: 151934 Hom.: 8110 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.291 AC: 44320 AN: 152052 Hom.: 8116 Cov.: 33 AF XY: 0.286 AC XY: 21297 AN XY: 74342

African (AFR) AF: 0.523 AC: 21664 AN: 41434

American (AMR) AF: 0.203 AC: 3095 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3470

East Asian (EAS) AF: 0.134 AC: 693 AN: 5174

South Asian (SAS) AF: 0.172 AC: 827 AN: 4820

European-Finnish (FIN) AF: 0.198 AC: 2096 AN: 10576

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14508 AN: 67986

Other (OTH) AF: 0.260 AC: 549 AN: 2112

Alfa AF: 0.232 Hom.: 19916

Bravo AF: 0.299

Asia WGS AF: 0.152 AC: 531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.7
DANN	Benign	0.60
PhyloP100		0.024
PromoterAI		-0.032	Neutral
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: rs11850957; hg19: chr14-25479542;