rs2297060

Positions:

• chr14-24812013-T-C
• chr14-24812013-T-G

Variant summary

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

The NM_001394410.1(STXBP6):​c.*696A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 152,132 control chromosomes in the GnomAD database, including 158 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 0.024 (158 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STXBP6 NM_001394410.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP6	NM_001394410.1	c.*696A>G		3_prime_UTR_variant	6/6	ENST00000323944.10	NP_001381339.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP6	ENST00000323944.10	c.*696A>G		3_prime_UTR_variant	6/6	1	NM_001394410.1	ENSP00000324302.5
STXBP6	ENST00000396700.5	c.*696A>G		3_prime_UTR_variant	7/7	1		ENSP00000379928.1

Frequencies

GnomAD3 genomes AF: 0.0235 AC: 3569 AN: 152014 Hom.: 154 Cov.: 32

Gnomad AFR AF: 0.00353

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.0890

Gnomad FIN AF: 0.0610

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0206

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0236 AC: 3583 AN: 152132 Hom.: 158 Cov.: 32 AF XY: 0.0272 AC XY: 2027 AN XY: 74400

Gnomad4 AFR AF: 0.00354

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.0889

Gnomad4 FIN AF: 0.0610

Gnomad4 NFE AF: 0.0153

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0147 Hom.: 24

Bravo AF: 0.0195

Asia WGS AF: 0.157 AC: 543 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.74

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: rs2297060; hg19: chr14-25281219;