rs4804218

Variant names:

• chr19-7634536-G-A
• rs4804218
• ENST00000698368.1:n.115-2279G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-7634536-G-A
• chr19-7634536-G-C

Variant summary

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

The NM_001414484.1(STXBP2):​c.-60+3690G>A 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 152,102 control chromosomes in the GnomAD database, including 7,151 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 (7151 hom., cov: 33)
• Consequence: STXBP2 NM_001414484.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414484.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP2	NM_001414484.1		c.-60+3690G>A		intron	N/A	NP_001401413.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000268400	ENST00000698368.1		n.115-2279G>A		intron	N/A	ENSP00000513686.1	A0A8V8TM65
	ENSG00000268400	ENST00000595866.2	TSL:5	n.138+3690G>A		intron	N/A	ENSP00000469553.2	M0QY33
	ENSG00000268400	ENST00000598664.5	TSL:5	n.51+3690G>A		intron	N/A	ENSP00000472796.1	M0R2T5

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44332 AN: 151982 Hom.: 7143 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.292 AC: 44353 AN: 152102 Hom.: 7151 Cov.: 33 AF XY: 0.292 AC XY: 21698 AN XY: 74336

African (AFR) AF: 0.165 AC: 6854 AN: 41502

American (AMR) AF: 0.246 AC: 3763 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 936 AN: 3472

East Asian (EAS) AF: 0.195 AC: 1011 AN: 5180

South Asian (SAS) AF: 0.287 AC: 1381 AN: 4820

European-Finnish (FIN) AF: 0.418 AC: 4411 AN: 10550

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

European-Non Finnish (NFE) AF: 0.369 AC: 25073 AN: 67978

Other (OTH) AF: 0.306 AC: 646 AN: 2112

Alfa AF: 0.197 Hom.: 456

Bravo AF: 0.272

Asia WGS AF: 0.249 AC: 868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.22
PhyloP100		-0.34

Splicing

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

Other links and lift over

dbSNP: rs4804218; hg19: chr19-7699422;