rs114127210

chr19-7647557-C-T

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.1696+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,570,170 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 0.013 (41 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (39 hom.)
• Consequence: STXBP2 NM_006949.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.94

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=-0.9).
• BP6: Variant 19-7647557-C-T is Benign according to our data. Variant chr19-7647557-C-T is described in ClinVar as [Benign]. Clinvar id is 260101.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1980/152156) while in subpopulation AFR AF= 0.0445 (1847/41518). AF 95% confidence interval is 0.0428. There are 41 homozygotes in gnomad4. There are 932 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP2	NM_006949.4	c.1696+46C>T		intron_variant		ENST00000221283.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP2	ENST00000221283.10	c.1696+46C>T		intron_variant		1	NM_006949.4	P4

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1972 AN: 152038 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00629

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00336 AC: 634 AN: 188622 Hom.: 6 AF XY: 0.00226 AC XY: 230 AN XY: 101890

Gnomad AFR exome AF: 0.0464

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.000124

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000158

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000237

Gnomad OTH exome AF: 0.00349

GnomAD4 exome AF: 0.00134 AC: 1901 AN: 1418014 Hom.: 39 Cov.: 36 AF XY: 0.00116 AC XY: 812 AN XY: 701966

Gnomad4 AFR exome AF: 0.0453

Gnomad4 AMR exome AF: 0.00239

Gnomad4 ASJ exome AF: 0.000243

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000183

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000790

Gnomad4 OTH exome AF: 0.00362

GnomAD4 genome AF: 0.0130 AC: 1980 AN: 152156 Hom.: 41 Cov.: 32 AF XY: 0.0125 AC XY: 932 AN XY: 74392

Gnomad4 AFR AF: 0.0445

Gnomad4 AMR AF: 0.00628

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: 0.00658 Hom.: 2

Bravo AF: 0.0153

Asia WGS AF: 0.00173 AC: 6 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	-0.90
Cadd	Benign	0.18
Dann	Benign	0.57
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs114127210; hg19: chr19-7712443;