rs768727082
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004750.5(CRLF1):c.713delC(p.Pro238ArgfsTer6) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,326 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
CRLF1
NM_004750.5 frameshift
NM_004750.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.88
Publications
6 publications found
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]
CRLF1 Gene-Disease associations (from GenCC):
- Cold-induced sweating syndrome 1Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- cold-induced sweating syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- idiopathic achalasiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 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 19-18597033-CG-C is Pathogenic according to our data. Variant chr19-18597033-CG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1676590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_004750.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CRLF1 | NM_004750.5 | MANE Select | c.713delC | p.Pro238ArgfsTer6 | frameshift | Exon 5 of 9 | NP_004741.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CRLF1 | ENST00000392386.8 | TSL:1 MANE Select | c.713delC | p.Pro238ArgfsTer6 | frameshift | Exon 5 of 9 | ENSP00000376188.2 | ||
| CRLF1 | ENST00000684169.1 | c.713delC | p.Pro238ArgfsTer6 | frameshift | Exon 5 of 9 | ENSP00000506849.1 | |||
| CRLF1 | ENST00000597131.1 | TSL:2 | c.176delC | p.Pro59fs | frameshift | Exon 2 of 4 | ENSP00000470625.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460326Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 726446 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1460326
Hom.:
Cov.:
33
AF XY:
AC XY:
2
AN XY:
726446
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33460
American (AMR)
AF:
AC:
0
AN:
44644
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26058
East Asian (EAS)
AF:
AC:
0
AN:
39678
South Asian (SAS)
AF:
AC:
0
AN:
86160
European-Finnish (FIN)
AF:
AC:
0
AN:
52764
Middle Eastern (MID)
AF:
AC:
1
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1111458
Other (OTH)
AF:
AC:
0
AN:
60338
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
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1
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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30-35
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
Cold-induced sweating syndrome 1 (2)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
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