rs137853926
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_004750.5(CRLF1):c.538C>T(p.Gln180Ter) 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 Lovd as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
CRLF1
NM_004750.5 stop_gained
NM_004750.5 stop_gained
Scores
3
3
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.16
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]
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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 19-18598591-G-A is Pathogenic according to our data. Variant chr19-18598591-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRLF1 | NM_004750.5 | c.538C>T | p.Gln180Ter | stop_gained | 4/9 | ENST00000392386.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRLF1 | ENST00000392386.8 | c.538C>T | p.Gln180Ter | stop_gained | 4/9 | 1 | NM_004750.5 | P1 | |
CRLF1 | ENST00000684169.1 | c.538C>T | p.Gln180Ter | stop_gained | 4/9 | ||||
CRLF1 | ENST00000597131.1 | c.4C>T | p.Gln2Ter | stop_gained | 1/4 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251064Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135710
GnomAD3 exomes
AF:
AC:
1
AN:
251064
Hom.:
AF XY:
AC XY:
1
AN XY:
135710
Gnomad AFR exome
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GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
AF:
AC:
1
EpiCase
AF:
EpiControl
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ClinVar
Not reported inComputational 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
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at