Variant rs2228260 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001079539.2(XBP1):c.207C>T(p.Pro69=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 1,555,012 control chromosomes in the GnomAD database, including 1,709 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 0.033 ( 169 hom., cov: 33)

Exomes 𝑓: 0.033 ( 1540 hom. )

Consequence

XBP1
NM_001079539.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.425

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP7

Synonymous conserved (PhyloP=-0.425 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0991 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.207C>T	p.Pro69=	synonymous_variant	1/6	ENST00000344347.6	NP_001073007.1
XBP1	NM_005080.4 linkuse as main transcript	c.207C>T	p.Pro69=	synonymous_variant	1/5		NP_005071.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XBP1	ENST00000344347.6 linkuse as main transcript	c.207C>T	p.Pro69=	synonymous_variant	1/6	5	NM_001079539.2	ENSP00000343155	P4	P17861-2
XBP1	ENST00000216037.10 linkuse as main transcript	c.207C>T	p.Pro69=	synonymous_variant	1/5	1		ENSP00000216037	A2	P17861-1
XBP1	ENST00000403532.7 linkuse as main transcript	c.207C>T	p.Pro69=	synonymous_variant	1/5	3		ENSP00000385162	A2
XBP1	ENST00000482720.1 linkuse as main transcript	n.252C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0329

AC:

4999

AN:

152168

Hom.:

167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00586

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0471

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0875

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0278

Gnomad OTH

AF:

0.0344

GnomAD3 exomes

AF:

0.0584

AC:

8813

AN:

150948

Hom.:

427

AF XY:

0.0578

AC XY:

4817

AN XY:

83308

show subpopulations

Gnomad AFR exome

AF:

0.00518

Gnomad AMR exome

AF:

0.0881

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.100

Gnomad SAS exome

AF:

0.0941

Gnomad FIN exome

AF:

0.0902

Gnomad NFE exome

AF:

0.0250

Gnomad OTH exome

AF:

0.0463

GnomAD4 exome

AF:

0.0332

AC:

46521

AN:

1402732

Hom.:

1540

Cov.:

AF XY:

0.0352

AC XY:

24392

AN XY:

693584

show subpopulations

Gnomad4 AFR exome

AF:

0.00387

Gnomad4 AMR exome

AF:

0.0811

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.113

Gnomad4 SAS exome

AF:

0.0931

Gnomad4 FIN exome

AF:

0.0931

Gnomad4 NFE exome

AF:

0.0230

Gnomad4 OTH exome

AF:

0.0353

GnomAD4 genome

AF:

0.0329

AC:

5010

AN:

152280

Hom.:

169

Cov.:

AF XY:

0.0374

AC XY:

2783

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00585

Gnomad4 AMR

AF:

0.0476

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.0875

Gnomad4 NFE

AF:

0.0278

Gnomad4 OTH

AF:

0.0383

Alfa

AF:

0.0255

Hom.:

Bravo

AF:

0.0259

Asia WGS

AF:

0.101

AC:

351

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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