19-7636780-C-A

Variant summary

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

The ENST00000601797.1(ENSG00000268204):n.211G>T 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 0.0517 in 228,606 control chromosomes in the GnomAD database, including 1,617 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (759 hom., cov: 32)
  • Exomes 𝑓: 0.061 (858 hom.)
• Consequence: ENST00000601797.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.963

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=-0.75).
• BP6: Variant 19-7636780-C-A is Benign according to our data. Variant chr19-7636780-C-A is described in ClinVar as [Benign]. Clinvar id is 1283193.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCP2	XM_006722639.4	c.-435G>T		5_prime_UTR_variant	1/4
STXBP2	NM_001414484.1	c.-59-1946C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000601797.1	n.211G>T		non_coding_transcript_exon_variant	1/2	3
STXBP2	ENST00000698369.1	n.9C>A		non_coding_transcript_exon_variant	1/17

Frequencies

GnomAD3 genomes AF: 0.0472 AC: 7179 AN: 152128 Hom.: 759 Cov.: 32

Gnomad AFR AF: 0.0343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.0825

Gnomad FIN AF: 0.0716

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0436

GnomAD4 exome AF: 0.0607 AC: 4633 AN: 76360 Hom.: 858 Cov.: 0 AF XY: 0.0557 AC XY: 2130 AN XY: 38274

Gnomad4 AFR exome AF: 0.0329

Gnomad4 AMR exome AF: 0.0833

Gnomad4 ASJ exome AF: 0.00733

Gnomad4 EAS exome AF: 0.491

Gnomad4 SAS exome AF: 0.0782

Gnomad4 FIN exome AF: 0.0585

Gnomad4 NFE exome AF: 0.00837

Gnomad4 OTH exome AF: 0.0466

GnomAD4 genome AF: 0.0472 AC: 7180 AN: 152246 Hom.: 759 Cov.: 32 AF XY: 0.0540 AC XY: 4022 AN XY: 74422

Gnomad4 AFR AF: 0.0343

Gnomad4 AMR AF: 0.0826

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.0828

Gnomad4 FIN AF: 0.0716

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.0436

Alfa AF: 0.0177 Hom.: 124

Bravo AF: 0.0483

Asia WGS AF: 0.244 AC: 845 AN: 3478

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	-0.75
Cadd	Benign	1.4
Dann	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2279043; hg19: chr19-7701666;