19-7639112-C-T

Variant names:

• chr19-7639112-C-T
• rs115239774
• NM_006949.4:c.169+12C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006949.4(STXBP2):​c.169+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,613,868 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0093 (23 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (21 hom.)
• Consequence: STXBP2 NM_006949.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.174

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-7639112-C-T is Benign according to our data. Variant chr19-7639112-C-T is described in ClinVar as [Benign]. Clinvar id is 260098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00934 (1423/152318) while in subpopulation AFR AF= 0.0311 (1294/41558). AF 95% confidence interval is 0.0297. There are 23 homozygotes in gnomad4. There are 689 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP2	NM_006949.4	c.169+12C>T		intron_variant	Intron 3 of 18	ENST00000221283.10	NP_008880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP2	ENST00000221283.10	c.169+12C>T		intron_variant	Intron 3 of 18	1	NM_006949.4	ENSP00000221283.4
ENSG00000268400	ENST00000698368.1	n.*272+12C>T		intron_variant	Intron 5 of 19			ENSP00000513686.1

Frequencies

GnomAD3 genomes AF: 0.00934 AC: 1421 AN: 152200 Hom.: 23 Cov.: 33

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00886

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00311 AC: 776 AN: 249568 Hom.: 7 AF XY: 0.00240 AC XY: 324 AN XY: 134954

Gnomad AFR exome AF: 0.0329

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00817

Gnomad SAS exome AF: 0.000589

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000107

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00116 AC: 1691 AN: 1461550 Hom.: 21 Cov.: 32 AF XY: 0.00103 AC XY: 746 AN XY: 727082

Gnomad4 AFR exome AF: 0.0330

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00529

Gnomad4 SAS exome AF: 0.000557

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000594

Gnomad4 OTH exome AF: 0.00262

GnomAD4 genome AF: 0.00934 AC: 1423 AN: 152318 Hom.: 23 Cov.: 33 AF XY: 0.00925 AC XY: 689 AN XY: 74480

Gnomad4 AFR AF: 0.0311

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00888

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.000553 Hom.: 0

Bravo AF: 0.0100

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial hemophagocytic lymphohistiocytosis 5 Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs115239774; hg19: chr19-7703998;