rs113694233

Variant names:

• chr19-7642064-C-T
• rs113694233
• NM_006949.4:c.609C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006949.4(STXBP2):​c.609C>T​(p.His203His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00079 in 1,614,076 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (8 hom.)
• Consequence: STXBP2 NM_006949.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.79

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]

ENSG00000268400 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-7642064-C-T is Benign according to our data. Variant chr19-7642064-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.79 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00351 (534/152298) while in subpopulation AFR AF= 0.0118 (491/41562). AF 95% confidence interval is 0.011. There are 5 homozygotes in gnomad4. There are 250 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP2	NM_006949.4	c.609C>T	p.His203His	synonymous_variant	Exon 8 of 19	ENST00000221283.10	NP_008880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP2	ENST00000221283.10	c.609C>T	p.His203His	synonymous_variant	Exon 8 of 19	1	NM_006949.4	ENSP00000221283.4
ENSG00000268400	ENST00000698368.1	n.*712C>T		non_coding_transcript_exon_variant	Exon 10 of 20			ENSP00000513686.1
ENSG00000268400	ENST00000698368.1	n.*712C>T		3_prime_UTR_variant	Exon 10 of 20			ENSP00000513686.1

Frequencies

GnomAD3 genomes AF: 0.00342 AC: 520 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.000926 AC: 232 AN: 250660 Hom.: 4 AF XY: 0.000759 AC XY: 103 AN XY: 135670

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000507 AC: 741 AN: 1461778 Hom.: 8 Cov.: 35 AF XY: 0.000458 AC XY: 333 AN XY: 727188

Gnomad4 AFR exome AF: 0.0119

Gnomad4 AMR exome AF: 0.000939

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000113

Gnomad4 OTH exome AF: 0.00204

GnomAD4 genome AF: 0.00351 AC: 534 AN: 152298 Hom.: 5 Cov.: 32 AF XY: 0.00336 AC XY: 250 AN XY: 74466

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00179 Hom.: 0

Bravo AF: 0.00368

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial hemophagocytic lymphohistiocytosis 5 Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

STXBP2: BP4, BP7, BS1, BS2 -

Autoinflammatory syndrome Benign:1

Jan 01, 2019

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Likely 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	-0.86
CADD	Benign	0.24
DANN	Benign	0.46

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: rs113694233; hg19: chr19-7706950;