ENST00000344347.6:c.95C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The ENST00000344347.6(XBP1):c.95C>T(p.Ala32Val) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

XBP1
ENST00000344347.6 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.785

Publications

1 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]

XBP1 links:

ENSG00000226471 (HGNC:):

ENSG00000226471 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07222423).

BP6

Variant 22-28800430-G-A is Benign according to our data. Variant chr22-28800430-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1255615.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000344347.6. 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	NM_001079539.2	MANE Select	c.95C>T	p.Ala32Val	missense	Exon 1 of 6	NP_001073007.1	P17861-2
	XBP1	NM_005080.4		c.95C>T	p.Ala32Val	missense	Exon 1 of 5	NP_005071.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
XBP1	ENST00000344347.6	TSL:5 MANE Select	c.95C>T	p.Ala32Val	missense	Exon 1 of 6	ENSP00000343155.5	P17861-2
XBP1	ENST00000216037.10	TSL:1	c.95C>T	p.Ala32Val	missense	Exon 1 of 5	ENSP00000216037.6	P17861-1
XBP1	ENST00000933819.1		c.95C>T	p.Ala32Val	missense	Exon 1 of 4	ENSP00000603878.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

77092

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1333664

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

657874

African (AFR)

AF:

0.00

AC:

AN:

26502

American (AMR)

AF:

0.00

AC:

AN:

24374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22552

East Asian (EAS)

AF:

0.00

AC:

AN:

30136

South Asian (SAS)

AF:

0.00

AC:

AN:

72550

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40264

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4936

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1057192

Other (OTH)

AF:

0.00

AC:

AN:

55158

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal dominant polycystic liver disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.5

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.46

M_CAP

Benign

0.085

MetaRNN

Benign

0.072

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

-0.79

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.28

REVEL

Benign

0.032

Sift

Benign

0.082

Sift4G

Benign

0.46

Polyphen

0.0030

Vest4

0.078

MutPred

0.17

Loss of relative solvent accessibility (P = 0.0404)

MVP

0.20

MPC

0.42

ClinPred

0.12

GERP RS

-0.020

PromoterAI

0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.041

gMVP

0.42

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over