19-7636862-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000601797.1(ENSG00000268204):n.129A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 367,426 control chromosomes in the GnomAD database, including 42,037 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (19506 hom., cov: 33)
  • Exomes 𝑓: 0.44 (22531 hom.)
• Consequence: ENST00000601797.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.628

Genes affected

(HGNC:):

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=-0.85).
• BP6: Variant 19-7636862-T-C is Benign according to our data. Variant chr19-7636862-T-C is described in ClinVar as [Benign]. Clinvar id is 1183758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCP2	XM_006722639.4	c.-517A>G		5_prime_UTR_variant	1/4
STXBP2	NM_001414484.1	c.-59-1864T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000601797.1	n.129A>G		non_coding_transcript_exon_variant	1/2	3
STXBP2	ENST00000698369.1	n.91T>C		non_coding_transcript_exon_variant	1/17

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74374 AN: 152010 Hom.: 19469 Cov.: 33

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.440 AC: 94675 AN: 215298 Hom.: 22531 Cov.: 0 AF XY: 0.436 AC XY: 47552 AN XY: 109090

Gnomad4 AFR exome AF: 0.661

Gnomad4 AMR exome AF: 0.488

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.752

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.513

Gnomad4 NFE exome AF: 0.381

Gnomad4 OTH exome AF: 0.442

GnomAD4 genome AF: 0.490 AC: 74469 AN: 152128 Hom.: 19506 Cov.: 33 AF XY: 0.495 AC XY: 36783 AN XY: 74374

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.465

Alfa AF: 0.391 Hom.: 11791

Bravo AF: 0.494

Asia WGS AF: 0.551 AC: 1917 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.3
Dann	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7359905; hg19: chr19-7701748;