rs137853928
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_004750.5(CRLF1):c.845_846del(p.Val282GlyfsTer47) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,172 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
CRLF1
NM_004750.5 frameshift
NM_004750.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.06
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 19-18596900-CCA-C is Pathogenic according to our data. Variant chr19-18596900-CCA-C is described in ClinVar as [Pathogenic]. Clinvar id is 224612.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-18596900-CCA-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRLF1 | NM_004750.5 | c.845_846del | p.Val282GlyfsTer47 | frameshift_variant | 5/9 | ENST00000392386.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRLF1 | ENST00000392386.8 | c.845_846del | p.Val282GlyfsTer47 | frameshift_variant | 5/9 | 1 | NM_004750.5 | P1 | |
CRLF1 | ENST00000597131.1 | c.310_311del | p.Val104GlyfsTer? | frameshift_variant | 2/4 | 2 | |||
CRLF1 | ENST00000684169.1 | c.845_846del | p.Val282GlyfsTer47 | frameshift_variant | 5/9 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1
AN:
152172
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74336
GnomAD4 genome
?
AF:
AC:
1
AN:
152172
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74336
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
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 | Feb 01, 2003 | - - |
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