GeneBe

rs775558575

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_147164.3(CNTFR):​c.505A>T​(p.Met169Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CNTFR
NM_147164.3 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21

Publications

0 publications found
Variant links:
Genes affected
CNTFR (HGNC:2170): (ciliary neurotrophic factor receptor) This gene encodes a member of the type 1 cytokine receptor family. The encoded protein is the ligand-specific component of a tripartite receptor for ciliary neurotrophic factor, which plays a critical role in neuronal cell survival, differentiation and gene expression. Binding of ciliary neurotrophic factor to the encoded protein recruits the transmembrane components of the receptor, gp130 and leukemia inhibitory factor receptor, facilitating signal transduction. Single nucleotide polymorphisms in this gene may be associated with variations in muscle strength, as well as early onset of eating disorders. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2011]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10641995).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147164.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
CNTFR
NM_147164.3
MANE Select
c.505A>Tp.Met169Leu
missense
Exon 6 of 10NP_671693.1P26992
CNTFR
NM_001207011.2
c.505A>Tp.Met169Leu
missense
Exon 6 of 10NP_001193940.1P26992
CNTFR
NM_001842.5
c.505A>Tp.Met169Leu
missense
Exon 5 of 9NP_001833.1P26992

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
CNTFR
ENST00000378980.8
TSL:1 MANE Select
c.505A>Tp.Met169Leu
missense
Exon 6 of 10ENSP00000368265.3P26992
CNTFR
ENST00000351266.8
TSL:1
c.505A>Tp.Met169Leu
missense
Exon 5 of 9ENSP00000242338.4P26992
CNTFR
ENST00000868706.1
c.505A>Tp.Met169Leu
missense
Exon 6 of 10ENSP00000538765.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
15
DANN
Benign
0.93
DEOGEN2
Benign
0.25
T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.31
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.69
N
PhyloP100
2.2
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.58
N
REVEL
Benign
0.033
Sift
Benign
0.28
T
Sift4G
Benign
0.78
T
Polyphen
0.0070
B
Vest4
0.30
MutPred
0.43
Gain of catalytic residue at M169 (P = 0.0351)
MVP
0.28
MPC
0.36
ClinPred
0.49
T
GERP RS
3.2
Varity_R
0.083
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs775558575; hg19: chr9-34557623; API