rs2303116

chr19-7641770-C-T

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.495C>T(p.Arg165=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,552,168 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (12 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (108 hom.)
• Consequence: STXBP2 NM_006949.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.671

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=-0.81).
• BP6: Variant 19-7641770-C-T is Benign according to our data. Variant chr19-7641770-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP2	NM_006949.4	c.495C>T	p.Arg165=	synonymous_variant	7/19	ENST00000221283.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP2	ENST00000221283.10	c.495C>T	p.Arg165=	synonymous_variant	7/19	1	NM_006949.4	P4

Frequencies

GnomAD3 genomes AF: 0.00303 AC: 461 AN: 152188 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0548

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00750 AC: 1182 AN: 157622 Hom.: 35 AF XY: 0.00804 AC XY: 668 AN XY: 83090

Gnomad AFR exome AF: 0.000786

Gnomad AMR exome AF: 0.000121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0597

Gnomad SAS exome AF: 0.0199

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000818

Gnomad OTH exome AF: 0.00584

GnomAD4 exome AF: 0.00291 AC: 4071 AN: 1399862 Hom.: 108 Cov.: 32 AF XY: 0.00334 AC XY: 2306 AN XY: 690606

Gnomad4 AFR exome AF: 0.000506

Gnomad4 AMR exome AF: 0.000140

Gnomad4 ASJ exome AF: 0.0000397

Gnomad4 EAS exome AF: 0.0528

Gnomad4 SAS exome AF: 0.0215

Gnomad4 FIN exome AF: 0.0000203

Gnomad4 NFE exome AF: 0.0000657

Gnomad4 OTH exome AF: 0.00633

GnomAD4 genome AF: 0.00301 AC: 458 AN: 152306 Hom.: 12 Cov.: 33 AF XY: 0.00349 AC XY: 260 AN XY: 74468

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0543

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.000579 Hom.: 1

Bravo AF: 0.00263

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Familial hemophagocytic lymphohistiocytosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Familial hemophagocytic lymphohistiocytosis 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 25, 2021

This variant is associated with the following publications: (PMID: 32517705) -

Autoinflammatory syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Feb 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.9
Dann	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2303116; hg19: chr19-7706656; COSMIC: COSV55401727; COSMIC: COSV55401727;