chr19-18594323-T-TA
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_004750.5(CRLF1):c.1135_1136insT(p.Tyr379LeufsTer115) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 29)
Consequence
CRLF1
NM_004750.5 frameshift
NM_004750.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.17
Genes affected
CRLF1 (HGNC:2364): (cytokine receptor like factor 1) This gene encodes a member of the cytokine type I receptor family. The protein forms a secreted complex with cardiotrophin-like cytokine factor 1 and acts on cells expressing ciliary neurotrophic factor receptors. The complex can promote survival of neuronal cells. Mutations in this gene result in Crisponi syndrome and cold-induced sweating syndrome. [provided by RefSeq, Oct 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 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;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRLF1 | NM_004750.5 | c.1135_1136insT | p.Tyr379LeufsTer115 | frameshift_variant | 7/9 | ENST00000392386.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRLF1 | ENST00000392386.8 | c.1135_1136insT | p.Tyr379LeufsTer115 | frameshift_variant | 7/9 | 1 | NM_004750.5 | P1 | |
CRLF1 | ENST00000684169.1 | c.1135_1136insT | p.Tyr379LeufsTer47 | frameshift_variant | 7/9 | ||||
CRLF1 | ENST00000594325.1 | n.112_113insT | non_coding_transcript_exon_variant | 1/3 | 3 | ||||
CRLF1 | ENST00000597131.1 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 29
GnomAD3 genomes
?
Cov.:
29
GnomAD4 exome Cov.: 37
GnomAD4 exome
Cov.:
37
GnomAD4 genome ? Cov.: 29
GnomAD4 genome
?
Cov.:
29
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 22, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation as the last 44 amino acids are replaced with 114 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.