ENST00000344347.6:c.573+103T>C
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000344347.6(XBP1):c.573+103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 1,504,106 control chromosomes in the GnomAD database, including 2,629 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 0.045 ( 204 hom., cov: 32)
Exomes 𝑓: 0.056 ( 2425 hom. )
Consequence
XBP1
ENST00000344347.6 intron
ENST00000344347.6 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.09
Publications
20 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]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
XBP1 | NM_001079539.2 | c.573+103T>C | intron_variant | Intron 5 of 5 | NP_001073007.1 | |||
XBP1 | NM_001393999.1 | c.423+103T>C | intron_variant | Intron 5 of 5 | NP_001380928.1 | |||
XBP1 | NM_005080.4 | c.599+103T>C | intron_variant | Intron 4 of 4 | NP_005071.2 | |||
XBP1 | NM_001394000.1 | c.449+103T>C | intron_variant | Intron 4 of 4 | NP_001380929.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0450 AC: 6848AN: 152172Hom.: 204 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
6848
AN:
152172
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0560 AC: 75662AN: 1351816Hom.: 2425 AF XY: 0.0552 AC XY: 37329AN XY: 676270 show subpopulations
GnomAD4 exome
AF:
AC:
75662
AN:
1351816
Hom.:
AF XY:
AC XY:
37329
AN XY:
676270
show subpopulations
African (AFR)
AF:
AC:
592
AN:
31348
American (AMR)
AF:
AC:
791
AN:
42370
Ashkenazi Jewish (ASJ)
AF:
AC:
304
AN:
24092
East Asian (EAS)
AF:
AC:
6
AN:
39166
South Asian (SAS)
AF:
AC:
2073
AN:
80470
European-Finnish (FIN)
AF:
AC:
3990
AN:
48566
Middle Eastern (MID)
AF:
AC:
87
AN:
5032
European-Non Finnish (NFE)
AF:
AC:
65181
AN:
1024094
Other (OTH)
AF:
AC:
2638
AN:
56678
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
3488
6975
10463
13950
17438
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.0450 AC: 6847AN: 152290Hom.: 204 Cov.: 32 AF XY: 0.0450 AC XY: 3354AN XY: 74466 show subpopulations
GnomAD4 genome
AF:
AC:
6847
AN:
152290
Hom.:
Cov.:
32
AF XY:
AC XY:
3354
AN XY:
74466
show subpopulations
African (AFR)
AF:
AC:
846
AN:
41572
American (AMR)
AF:
AC:
391
AN:
15298
Ashkenazi Jewish (ASJ)
AF:
AC:
63
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5180
South Asian (SAS)
AF:
AC:
150
AN:
4832
European-Finnish (FIN)
AF:
AC:
903
AN:
10610
Middle Eastern (MID)
AF:
AC:
2
AN:
294
European-Non Finnish (NFE)
AF:
AC:
4431
AN:
68008
Other (OTH)
AF:
AC:
59
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
342
684
1025
1367
1709
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
38
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
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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