rs4804217

Variant names:

• chr19-7634461-C-T
• rs4804217
• ENST00000698368.1:n.115-2354C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000698368.1(ENSG00000268400):​n.115-2354C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,192 control chromosomes in the GnomAD database, including 7,199 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (7199 hom., cov: 33)
• Consequence: ENSG00000268400 ENST00000698368.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848
• Publications: 18 publications found

Genes affected

ENSG00000268400 (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]

PCP2 (HGNC:30209): (Purkinje cell protein 2) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to act upstream of or within rhodopsin mediated signaling pathway. Predicted to be located in neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP2	NM_001414484.1	c.-60+3615C>T		intron_variant	Intron 3 of 20		NP_001401413.1
PCP2	XM_006722639.4	c.-60-1631G>A		intron_variant	Intron 1 of 3		XP_006722702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000268400	ENST00000698368.1	n.115-2354C>T		intron_variant	Intron 2 of 19			ENSP00000513686.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44415 AN: 152074 Hom.: 7191 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.302

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44438 AN: 152192 Hom.: 7199 Cov.: 33 AF XY: 0.292 AC XY: 21738 AN XY: 74398

African (AFR) AF: 0.165 AC: 6836 AN: 41528

American (AMR) AF: 0.248 AC: 3786 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3470

East Asian (EAS) AF: 0.186 AC: 964 AN: 5176

South Asian (SAS) AF: 0.288 AC: 1391 AN: 4822

European-Finnish (FIN) AF: 0.418 AC: 4426 AN: 10584

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25161 AN: 68010

Other (OTH) AF: 0.307 AC: 648 AN: 2114

Alfa AF: 0.331 Hom.: 18022

Bravo AF: 0.272

Asia WGS AF: 0.242 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.33
PhyloP100		-0.85

Splicing

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

Other links and lift over

dbSNP: rs4804217; hg19: chr19-7699347;