rs115668246

Positions:

• chr19-7638696-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006949.4(STXBP2):​c.38-30A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,613,714 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (38 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (42 hom.)
• Consequence: STXBP2 NM_006949.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.298

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-7638696-A-C is Benign according to our data. Variant chr19-7638696-A-C is described in ClinVar as [Benign]. Clinvar id is 260103.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1879/152086) while in subpopulation AFR AF= 0.0422 (1750/41462). AF 95% confidence interval is 0.0406. There are 38 homozygotes in gnomad4. There are 887 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP2	NM_006949.4	c.38-30A>C		intron_variant		ENST00000221283.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP2	ENST00000221283.10	c.38-30A>C		intron_variant		1	NM_006949.4	P4

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1874 AN: 151994 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00603

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00326 AC: 820 AN: 251460 Hom.: 10 AF XY: 0.00229 AC XY: 311 AN XY: 135912

Gnomad AFR exome AF: 0.0437

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00133 AC: 1950 AN: 1461628 Hom.: 42 Cov.: 30 AF XY: 0.00114 AC XY: 830 AN XY: 727148

Gnomad4 AFR exome AF: 0.0441

Gnomad4 AMR exome AF: 0.00233

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000738

Gnomad4 OTH exome AF: 0.00358

GnomAD4 genome AF: 0.0124 AC: 1879 AN: 152086 Hom.: 38 Cov.: 32 AF XY: 0.0119 AC XY: 887 AN XY: 74352

Gnomad4 AFR AF: 0.0422

Gnomad4 AMR AF: 0.00602

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00614 Hom.: 1

Bravo AF: 0.0147

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs115668246; hg19: chr19-7703582;