11-58624449-G-A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_000614.4(CNTF):c.530G>A(p.Arg177His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
CNTF
NM_000614.4 missense
NM_000614.4 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 2.21
Publications
2 publications found
Genes affected
CNTF (HGNC:2169): (ciliary neurotrophic factor) The protein encoded by this gene is a polypeptide hormone whose actions appear to be restricted to the nervous system where it promotes neurotransmitter synthesis and neurite outgrowth in certain neuronal populations. The protein is a potent survival factor for neurons and oligodendrocytes and may be relevant in reducing tissue destruction during inflammatory attacks. A mutation in this gene, which results in aberrant splicing, leads to ciliary neurotrophic factor deficiency, but this phenotype is not causally related to neurologic disease. A read-through transcript variant composed of the upstream ZFP91 gene and CNTF sequence has been identified, but it is thought to be non-coding. Read-through transcription of ZFP91 and CNTF has also been observed in mouse. [provided by RefSeq, Oct 2010]
ZFP91-CNTF (HGNC:33441): (ZFP91-CNTF readthrough (NMD candidate)) This gene represents a read-through transcript composed of ZFP91 and CNTF sequence. This transcript is thought to be non-coding because it would be subject to nonsense-mediated mRNA decay (NMD). Read-through transcription of ZFP91 and CNTF has also been observed in mouse. [provided by RefSeq, Aug 2008]
Genome browser will be placed here
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;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000614.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CNTF | TSL:1 MANE Select | c.530G>A | p.Arg177His | missense | Exon 2 of 2 | ENSP00000355370.4 | P26441 | ||
| ZFP91-CNTF | TSL:2 | n.*502G>A | non_coding_transcript_exon | Exon 13 of 13 | ENSP00000455911.1 | ||||
| ZFP91-CNTF | TSL:2 | n.*502G>A | 3_prime_UTR | Exon 13 of 13 | ENSP00000455911.1 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152028Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152028
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:
GnomAD2 exomes AF: 0.0000161 AC: 4AN: 248380 AF XY: 0.00000744 show subpopulations
GnomAD2 exomes
AF:
AC:
4
AN:
248380
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461782Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727200 show subpopulations
GnomAD4 exome
AF:
AC:
25
AN:
1461782
Hom.:
Cov.:
32
AF XY:
AC XY:
10
AN XY:
727200
show subpopulations
African (AFR)
AF:
AC:
2
AN:
33472
American (AMR)
AF:
AC:
0
AN:
44710
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26124
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
3
AN:
86252
European-Finnish (FIN)
AF:
AC:
1
AN:
53412
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
19
AN:
1111956
Other (OTH)
AF:
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
2
3
5
6
8
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 0.00000658 AC: 1AN: 152028Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74260 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152028
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74260
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41398
American (AMR)
AF:
AC:
0
AN:
15254
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
1
AN:
4814
European-Finnish (FIN)
AF:
AC:
0
AN:
10584
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68008
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ExAC
AF:
AC:
4
EpiCase
AF:
EpiControl
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Benign
T
PROVEAN
Uncertain
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0362)
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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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