22-28795210-CAA-C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_001079539.2(XBP1):c.1094_1095delTT(p.Phe365CysfsTer3) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.3e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
XBP1
NM_001079539.2 frameshift
NM_001079539.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.53
Publications
0 publications found
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: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001079539.2. 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 |
|---|---|---|---|---|---|---|---|---|---|
| XBP1 | MANE Select | c.1094_1095delTT | p.Phe365CysfsTer3 | frameshift | Exon 6 of 6 | NP_001073007.1 | P17861-2 | ||
| XBP1 | c.944_945delTT | p.Phe315CysfsTer3 | frameshift | Exon 6 of 6 | NP_001380928.1 | ||||
| XBP1 | c.*334_*335delTT | 3_prime_UTR | Exon 5 of 5 | NP_005071.2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| XBP1 | TSL:5 MANE Select | c.1094_1095delTT | p.Phe365CysfsTer3 | frameshift | Exon 6 of 6 | ENSP00000343155.5 | P17861-2 | ||
| XBP1 | TSL:1 | c.*334_*335delTT | 3_prime_UTR | Exon 5 of 5 | ENSP00000216037.6 | P17861-1 | |||
| XBP1 | c.974_975delTT | p.Phe325CysfsTer3 | frameshift | Exon 4 of 4 | ENSP00000603878.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.27e-7 AC: 1AN: 1376358Hom.: 0 AF XY: 0.00000148 AC XY: 1AN XY: 677024 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1376358
Hom.:
AF XY:
AC XY:
1
AN XY:
677024
show subpopulations
African (AFR)
AF:
AC:
0
AN:
30942
American (AMR)
AF:
AC:
0
AN:
32126
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
23044
East Asian (EAS)
AF:
AC:
0
AN:
35750
South Asian (SAS)
AF:
AC:
0
AN:
74748
European-Finnish (FIN)
AF:
AC:
0
AN:
48410
Middle Eastern (MID)
AF:
AC:
0
AN:
5554
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1068776
Other (OTH)
AF:
AC:
0
AN:
57008
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
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55-60
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Other
Revision:
Pathogenic
VUS
Benign
Condition
-
-
-
Neoplasm (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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