rs28464386

Variant names:

• chr19-7647822-G-A
• rs28464386
• NM_006949.4:c.*12G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-7647822-G-A
• chr19-7647822-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006949.4(STXBP2):​c.*12G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 1,344,010 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (97 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (105 hom.)
• Consequence: STXBP2 NM_006949.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.528

Genes affected

STXBP2 (HGNC:11445): (syntaxin binding protein 2) This gene encodes a member of the STXBP/unc-18/SEC1 family. The encoded protein is involved in intracellular trafficking, control of SNARE (soluble NSF attachment protein receptor) complex assembly, and the release of cytotoxic granules by natural killer cells. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-7647822-G-A is Benign according to our data. Variant chr19-7647822-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP2	NM_006949.4	c.*12G>A		3_prime_UTR_variant	Exon 19 of 19	ENST00000221283.10	NP_008880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP2	ENST00000221283.10	c.*12G>A		3_prime_UTR_variant	Exon 19 of 19	1	NM_006949.4	ENSP00000221283.4

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3229 AN: 144248 Hom.: 97 Cov.: 32

Gnomad AFR AF: 0.0759

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00948

Gnomad ASJ AF: 0.00119

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000473

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.000718

Gnomad OTH AF: 0.0126

GnomAD3 exomes AF: 0.00606 AC: 1512 AN: 249452 Hom.: 54 AF XY: 0.00452 AC XY: 611 AN XY: 135084

Gnomad AFR exome AF: 0.0760

Gnomad AMR exome AF: 0.00542

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000605

Gnomad OTH exome AF: 0.00295

GnomAD4 exome AF: 0.00305 AC: 3663 AN: 1199644 Hom.: 105 Cov.: 32 AF XY: 0.00269 AC XY: 1612 AN XY: 598940

Gnomad4 AFR exome AF: 0.0919

Gnomad4 AMR exome AF: 0.00600

Gnomad4 ASJ exome AF: 0.00184

Gnomad4 EAS exome AF: 0.0000446

Gnomad4 SAS exome AF: 0.000194

Gnomad4 FIN exome AF: 0.0000539

Gnomad4 NFE exome AF: 0.000503

Gnomad4 OTH exome AF: 0.00704

GnomAD4 genome AF: 0.0224 AC: 3236 AN: 144366 Hom.: 97 Cov.: 32 AF XY: 0.0217 AC XY: 1520 AN XY: 70158

Gnomad4 AFR AF: 0.0759

Gnomad4 AMR AF: 0.00946

Gnomad4 ASJ AF: 0.00119

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000473

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000718

Gnomad4 OTH AF: 0.0125

Alfa AF: 0.00227 Hom.: 1

Bravo AF: 0.0241

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Sep 23, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 10, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27884173, 21881043) -

Familial hemophagocytic lymphohistiocytosis 5 Benign:2

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autoinflammatory syndrome Benign:1

Aug 12, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.83
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs28464386; hg19: chr19-7712708;