chr9-34564745-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_147164.3(CNTFR):​c.173G>A​(p.Arg58Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

CNTFR
NM_147164.3 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.12
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.115326405).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNTFRNM_147164.3 linkc.173G>A p.Arg58Gln missense_variant Exon 4 of 10 ENST00000378980.8 NP_671693.1 P26992

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNTFRENST00000378980.8 linkc.173G>A p.Arg58Gln missense_variant Exon 4 of 10 1 NM_147164.3 ENSP00000368265.3 P26992
CNTFRENST00000351266.8 linkc.173G>A p.Arg58Gln missense_variant Exon 3 of 9 1 ENSP00000242338.4 P26992
CNTFRENST00000610543.4 linkc.173G>A p.Arg58Gln missense_variant Exon 4 of 10 5 ENSP00000480451.1 P26992
CNTFRENST00000417345.2 linkc.173G>A p.Arg58Gln missense_variant Exon 4 of 7 3 ENSP00000388082.1 Q5T8H6

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152074
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000557
AC:
14
AN:
251220
Hom.:
0
AF XY:
0.0000663
AC XY:
9
AN XY:
135816
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000301
AC:
44
AN:
1461884
Hom.:
0
Cov.:
32
AF XY:
0.0000371
AC XY:
27
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.000358
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152192
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.000337
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000772
Hom.:
0
Bravo
AF:
0.0000982
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000741
AC:
9
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.173G>A (p.R58Q) alteration is located in exon 4 (coding exon 2) of the CNTFR gene. This alteration results from a G to A substitution at nucleotide position 173, causing the arginine (R) at amino acid position 58 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T;T;T;T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.43
N
LIST_S2
Uncertain
0.87
.;.;D;D
M_CAP
Benign
0.050
D
MetaRNN
Benign
0.12
T;T;T;T
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
1.6
L;L;L;.
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.6
N;N;.;N
REVEL
Benign
0.12
Sift
Benign
0.31
T;T;.;T
Sift4G
Benign
0.34
T;T;T;T
Polyphen
0.72
P;P;P;.
Vest4
0.099
MVP
0.61
MPC
0.51
ClinPred
0.042
T
GERP RS
2.2
Varity_R
0.073
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs151167190; hg19: chr9-34564743; API