rs55954306

Variant names:

• chr19-7647275-C-T
• rs55954306
• NM_006949.4:c.1538+28C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006949.4(STXBP2):​c.1538+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,610,808 control chromosomes in the GnomAD database, including 14,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.098 (970 hom., cov: 34)
  • Exomes 𝑓: 0.13 (13403 hom.)
• Consequence: STXBP2 NM_006949.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.42
• Publications: 7 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-7647275-C-T is Benign according to our data. Variant chr19-7647275-C-T is described in ClinVar as Benign. ClinVar VariationId is 260092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

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.1538+28C>T		intron	N/A	NP_008880.2	Q15833-1
	STXBP2	NM_001272034.2		c.1571+28C>T		intron	N/A	NP_001258963.1	Q15833-3
	STXBP2	NM_001127396.3		c.1529+28C>T		intron	N/A	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.1538+28C>T		intron	N/A	ENSP00000221283.4	Q15833-1
	STXBP2	ENST00000414284.6	TSL:1	c.1529+28C>T		intron	N/A	ENSP00000409471.1	Q15833-2
	STXBP2	ENST00000597068.5	TSL:1	n.*286+28C>T		intron	N/A	ENSP00000471327.1	M0R0M7

Frequencies

GnomAD3 genomes AF: 0.0983 AC: 14957 AN: 152136 Hom.: 970 Cov.: 34

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0979

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0412

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.103 AC: 24254 AN: 236208 AF XY: 0.103

Gnomad AFR exome AF: 0.0248

Gnomad AMR exome AF: 0.0861

Gnomad ASJ exome AF: 0.0897

Gnomad EAS exome AF: 0.000680

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.129 AC: 188743 AN: 1458554 Hom.: 13403 Cov.: 31 AF XY: 0.127 AC XY: 92347 AN XY: 725650

African (AFR) AF: 0.0210 AC: 704 AN: 33446

American (AMR) AF: 0.0874 AC: 3902 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.0919 AC: 2398 AN: 26082

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39688

South Asian (SAS) AF: 0.0420 AC: 3619 AN: 86198

European-Finnish (FIN) AF: 0.149 AC: 7635 AN: 51124

Middle Eastern (MID) AF: 0.0930 AC: 524 AN: 5636

European-Non Finnish (NFE) AF: 0.147 AC: 162991 AN: 1111412

Other (OTH) AF: 0.115 AC: 6960 AN: 60300

GnomAD4 genome AF: 0.0982 AC: 14956 AN: 152254 Hom.: 970 Cov.: 34 AF XY: 0.0978 AC XY: 7279 AN XY: 74448

African (AFR) AF: 0.0253 AC: 1050 AN: 41574

American (AMR) AF: 0.0977 AC: 1495 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5166

South Asian (SAS) AF: 0.0422 AC: 204 AN: 4830

European-Finnish (FIN) AF: 0.148 AC: 1573 AN: 10612

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9968 AN: 67982

Other (OTH) AF: 0.111 AC: 234 AN: 2114

Alfa AF: 0.116 Hom.: 229

Bravo AF: 0.0937

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.53
DANN	Benign	0.82
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs55954306; hg19: chr19-7712161; COSMIC: COSV55404266; COSMIC: COSV55404266;