rs139160342

Variant names:

• chr19-7644673-C-A
• rs139160342
• NM_006949.4:c.1167C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-7644673-C-A
• chr19-7644673-C-T
• chr19-7644673-C-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_006949.4(STXBP2):​c.1167C>A​(p.Ile389Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. I389I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: STXBP2 NM_006949.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48
• Publications: 3 publications found

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]

STXBP2 Gene-Disease associations (from GenCC):

• familial hemophagocytic lymphohistiocytosis 5

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hereditary hemophagocytic lymphohistiocytosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• microvillus inclusion disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000268400 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 19-7644673-C-A is Benign according to our data. Variant chr19-7644673-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1135894.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.48 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006949.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP2	NM_006949.4	MANE Select	c.1167C>A	p.Ile389Ile	synonymous	Exon 14 of 19	NP_008880.2	Q15833-1
	STXBP2	NM_001272034.2		c.1200C>A	p.Ile400Ile	synonymous	Exon 14 of 19	NP_001258963.1	Q15833-3
	STXBP2	NM_001127396.3		c.1158C>A	p.Ile386Ile	synonymous	Exon 14 of 19	NP_001120868.1	Q15833-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP2	ENST00000221283.10	TSL:1 MANE Select	c.1167C>A	p.Ile389Ile	synonymous	Exon 14 of 19	ENSP00000221283.4	Q15833-1
	STXBP2	ENST00000414284.6	TSL:1	c.1158C>A	p.Ile386Ile	synonymous	Exon 14 of 19	ENSP00000409471.1	Q15833-2
	STXBP2	ENST00000597068.5	TSL:1	n.1086C>A		non_coding_transcript_exon	Exon 13 of 19	ENSP00000471327.1	M0R0M7

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152096 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 250798 AF XY: 0.00000737

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461494 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727068

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111852

Other (OTH) AF: 0.0000166 AC: 1 AN: 60380

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152096 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74286

African (AFR) AF: 0.0000966 AC: 4 AN: 41392

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Familial hemophagocytic lymphohistiocytosis 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	0.22
DANN	Benign	0.79
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs139160342; hg19: chr19-7709559;