rs121912501
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001127671.2(LIFR):c.1789C>T(p.Arg597Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001127671.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIFR | NM_001127671.2 | c.1789C>T | p.Arg597Ter | stop_gained | 13/20 | ENST00000453190.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIFR | ENST00000453190.7 | c.1789C>T | p.Arg597Ter | stop_gained | 13/20 | 2 | NM_001127671.2 | P1 | |
LIFR | ENST00000263409.8 | c.1789C>T | p.Arg597Ter | stop_gained | 13/20 | 1 | P1 | ||
LIFR | ENST00000503088.1 | n.1952C>T | non_coding_transcript_exon_variant | 13/15 | 1 | ||||
LIFR | ENST00000506003.5 | c.168C>T | p.Tyr56= | synonymous_variant, NMD_transcript_variant | 3/7 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251466Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135904
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461618Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727148
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152272Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74452
ClinVar
Submissions by phenotype
Stuve-Wiedemann syndrome Pathogenic:3
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2004 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Jul 08, 2020 | - - |
Pathogenic, no assertion criteria provided | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | - | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2023 | This sequence change creates a premature translational stop signal (p.Arg597*) in the LIFR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LIFR are known to be pathogenic (PMID: 14740318). This variant is present in population databases (rs121912501, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with Stuve-Wiedemann syndrome (PMID: 14740318). ClinVar contains an entry for this variant (Variation ID: 14460). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at