GeneBe

rs2239815

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000344347.6(XBP1):​c.453+395A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

XBP1
ENST00000344347.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0440

Publications

46 publications found
Variant links:
Genes affected
XBP1 (HGNC:12801): (X-box binding protein 1) This gene encodes a transcription factor that regulates MHC class II genes by binding to a promoter element referred to as an X box. This gene product is a bZIP protein, which was also identified as a cellular transcription factor that binds to an enhancer in the promoter of the T cell leukemia virus type 1 promoter. It may increase expression of viral proteins by acting as the DNA binding partner of a viral transactivator. It has been found that upon accumulation of unfolded proteins in the endoplasmic reticulum (ER), the mRNA of this gene is processed to an active form by an unconventional splicing mechanism that is mediated by the endonuclease inositol-requiring enzyme 1 (IRE1). The resulting loss of 26 nt from the spliced mRNA causes a frame-shift and an isoform XBP1(S), which is the functionally active transcription factor. The isoform encoded by the unspliced mRNA, XBP1(U), is constitutively expressed, and thought to function as a negative feedback regulator of XBP1(S), which shuts off transcription of target genes during the recovery phase of ER stress. A pseudogene of XBP1 has been identified and localized to chromosome 5. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
XBP1NM_001079539.2 linkc.453+395A>T intron_variant Intron 3 of 5 NP_001073007.1 P17861-2
XBP1NM_001393999.1 linkc.303+395A>T intron_variant Intron 3 of 5 NP_001380928.1
XBP1NM_005080.4 linkc.453+395A>T intron_variant Intron 3 of 4 NP_005071.2 P17861-1A0A024R1F0
XBP1NM_001394000.1 linkc.303+395A>T intron_variant Intron 3 of 4 NP_001380929.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
XBP1ENST00000344347.6 linkc.453+395A>T intron_variant Intron 3 of 5 5 ENSP00000343155.5 P17861-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
21698
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
11182
African (AFR)
AF:
0.00
AC:
0
AN:
406
American (AMR)
AF:
0.00
AC:
0
AN:
1420
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
570
East Asian (EAS)
AF:
0.00
AC:
0
AN:
562
South Asian (SAS)
AF:
0.00
AC:
0
AN:
1686
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
938
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
80
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
14674
Other (OTH)
AF:
0.00
AC:
0
AN:
1362
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
3.9
DANN
Benign
0.84
PhyloP100
-0.044

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs2239815; hg19: chr22-29192670; API