GeneBe

NM_004750.5:c.75_77dupGCT

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004750.5(CRLF1):​c.75_77dupGCT​(p.Leu26dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000705 in 992,356 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 21)
Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

CRLF1
NM_004750.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

5 publications found
Variant links:
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 1
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • cold-induced sweating syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • idiopathic achalasia
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRLF1NM_004750.5 linkc.75_77dupGCT p.Leu26dup disruptive_inframe_insertion Exon 1 of 9 ENST00000392386.8 NP_004741.1 O75462

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRLF1ENST00000392386.8 linkc.75_77dupGCT p.Leu26dup disruptive_inframe_insertion Exon 1 of 9 1 NM_004750.5 ENSP00000376188.2 O75462
CRLF1ENST00000684169.1 linkc.75_77dupGCT p.Leu26dup disruptive_inframe_insertion Exon 1 of 9 ENSP00000506849.1 A0A804HI12
CRLF1ENST00000593286.1 linkn.367+793_367+795dupGCT intron_variant Intron 1 of 1 4

Frequencies

GnomAD3 genomes
Cov.:
21
GnomAD4 exome
AF:
0.00000705
AC:
7
AN:
992356
Hom.:
0
Cov.:
0
AF XY:
0.0000129
AC XY:
6
AN XY:
466884
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
19976
American (AMR)
AF:
0.00
AC:
0
AN:
5100
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
11030
East Asian (EAS)
AF:
0.00
AC:
0
AN:
18430
South Asian (SAS)
AF:
0.000214
AC:
4
AN:
18694
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
14482
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2498
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
864780
Other (OTH)
AF:
0.0000803
AC:
3
AN:
37366
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.589
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
21
Alfa
AF:
0.00
Hom.:
192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs34503316; hg19: chr19-18717389; API