Variant rs2269575 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001079539.2(XBP1):c.-14C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0727 in 1,475,272 control chromosomes in the GnomAD database, including 6,027 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 0.12 ( 1520 hom., cov: 34)

Exomes 𝑓: 0.068 ( 4507 hom. )

Consequence

XBP1
NM_001079539.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

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]

XBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XBP1	NM_001079539.2 linkuse as main transcript	c.-14C>T		5_prime_UTR_variant	1/6	ENST00000344347.6	NP_001073007.1
XBP1	NM_005080.4 linkuse as main transcript	c.-14C>T		5_prime_UTR_variant	1/5		NP_005071.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XBP1	ENST00000344347.6 linkuse as main transcript	c.-14C>T	5_prime_UTR_variant	1/6	5	NM_001079539.2	ENSP00000343155	P4	P17861-2
XBP1	ENST00000216037.10 linkuse as main transcript	c.-14C>T	5_prime_UTR_variant	1/5	1		ENSP00000216037	A2	P17861-1
XBP1	ENST00000403532.7 linkuse as main transcript	c.-14C>T	5_prime_UTR_variant	1/5	3		ENSP00000385162	A2
XBP1	ENST00000482720.1 linkuse as main transcript	n.32C>T	non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17696

AN:

152112

Hom.:

1514

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0709

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.0654

Gnomad FIN

AF:

0.0726

Gnomad MID

AF:

0.0764

Gnomad NFE

AF:

0.0542

Gnomad OTH

AF:

0.0970

GnomAD3 exomes

AF:

0.0885

AC:

6444

AN:

72794

Hom.:

401

AF XY:

0.0811

AC XY:

3444

AN XY:

42466

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.0703

Gnomad EAS exome

AF:

0.281

Gnomad SAS exome

AF:

0.0576

Gnomad FIN exome

AF:

0.0699

Gnomad NFE exome

AF:

0.0552

Gnomad OTH exome

AF:

0.0763

GnomAD4 exome

AF:

0.0676

AC:

89450

AN:

1323052

Hom.:

4507

Cov.:

AF XY:

0.0662

AC XY:

43202

AN XY:

652586

show subpopulations

Gnomad4 AFR exome

AF:

0.232

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.0630

Gnomad4 EAS exome

AF:

0.302

Gnomad4 SAS exome

AF:

0.0585

Gnomad4 FIN exome

AF:

0.0609

Gnomad4 NFE exome

AF:

0.0555

Gnomad4 OTH exome

AF:

0.0829

GnomAD4 genome

AF:

0.117

AC:

17742

AN:

152220

Hom.:

1520

Cov.:

AF XY:

0.116

AC XY:

8651

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.227

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.0709

Gnomad4 EAS

AF:

0.277

Gnomad4 SAS

AF:

0.0656

Gnomad4 FIN

AF:

0.0726

Gnomad4 NFE

AF:

0.0542

Gnomad4 OTH

AF:

0.100

Alfa

AF:

0.0285

Hom.:

Bravo

AF:

0.126

Asia WGS

AF:

0.186

AC:

642

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.1

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over