rs1114167358
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001127671.2(LIFR):c.1273_1276del(p.Val425IlefsTer2) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
LIFR
NM_001127671.2 frameshift
NM_001127671.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.89
Genes affected
LIFR (HGNC:6597): (LIF receptor subunit alpha) This gene encodes a protein that belongs to the type I cytokine receptor family. This protein combines with a high-affinity converter subunit, gp130, to form a receptor complex that mediates the action of the leukemia inhibitory factor, a polyfunctional cytokine that is involved in cellular differentiation, proliferation and survival in the adult and the embryo. Mutations in this gene cause Schwartz-Jampel syndrome type 2, a disease belonging to the group of the bent-bone dysplasias. A translocation that involves the promoter of this gene, t(5;8)(p13;q12) with the pleiomorphic adenoma gene 1, is associated with salivary gland pleiomorphic adenoma, a common type of benign epithelial tumor of the salivary gland. Multiple splice variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2018]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-38505919-TTAAC-T is Pathogenic according to our data. Variant chr5-38505919-TTAAC-T is described in ClinVar as [Pathogenic]. Clinvar id is 369648.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIFR | NM_001127671.2 | c.1273_1276del | p.Val425IlefsTer2 | frameshift_variant | 9/20 | ENST00000453190.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIFR | ENST00000453190.7 | c.1273_1276del | p.Val425IlefsTer2 | frameshift_variant | 9/20 | 2 | NM_001127671.2 | P1 | |
LIFR | ENST00000263409.8 | c.1273_1276del | p.Val425IlefsTer2 | frameshift_variant | 9/20 | 1 | P1 | ||
LIFR | ENST00000503088.1 | n.1436_1439del | non_coding_transcript_exon_variant | 9/15 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital anomaly of kidney and urinary tract Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Weber Lab, Hannover Medical School | Sep 14, 2016 | - - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at