19-18594357-T-A
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_004750.5(CRLF1):c.1102A>T(p.Lys368Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 29)
Consequence
CRLF1
NM_004750.5 stop_gained
NM_004750.5 stop_gained
Scores
3
2
2
Clinical Significance
Conservation
PhyloP100: 4.16
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 11 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 19-18594357-T-A is Pathogenic according to our data. Variant chr19-18594357-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 5711.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-18594357-T-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRLF1 | NM_004750.5 | c.1102A>T | p.Lys368Ter | stop_gained | 7/9 | ENST00000392386.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRLF1 | ENST00000392386.8 | c.1102A>T | p.Lys368Ter | stop_gained | 7/9 | 1 | NM_004750.5 | P1 | |
CRLF1 | ENST00000684169.1 | c.1102A>T | p.Lys368Ter | stop_gained | 7/9 | ||||
CRLF1 | ENST00000594325.1 | n.79A>T | 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: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Cold-induced sweating syndrome 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2007 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
MutationTaster
Benign
A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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