9-34552180-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.1099G>A​(p.Ala367Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,595,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CNTFR
NM_147164.3 missense

Scores

2
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.835
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=0.100922406).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNTFRNM_147164.3 linkc.1099G>A p.Ala367Thr missense_variant Exon 9 of 10 ENST00000378980.8 NP_671693.1 P26992

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNTFRENST00000378980.8 linkc.1099G>A p.Ala367Thr missense_variant Exon 9 of 10 1 NM_147164.3 ENSP00000368265.3 P26992
CNTFRENST00000351266.8 linkc.1099G>A p.Ala367Thr missense_variant Exon 8 of 9 1 ENSP00000242338.4 P26992
CNTFRENST00000610543.4 linkc.1099G>A p.Ala367Thr missense_variant Exon 9 of 10 5 ENSP00000480451.1 P26992

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152086
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000373
AC:
8
AN:
214324
Hom.:
0
AF XY:
0.0000429
AC XY:
5
AN XY:
116512
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000293
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000132
AC:
19
AN:
1443762
Hom.:
0
Cov.:
32
AF XY:
0.0000126
AC XY:
9
AN XY:
716348
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000237
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000168
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.0000336
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152086
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000167
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1099G>A (p.A367T) alteration is located in exon 9 (coding exon 7) of the CNTFR gene. This alteration results from a G to A substitution at nucleotide position 1099, causing the alanine (A) at amino acid position 367 to be replaced by a threonine (T). 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
0.092
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.31
T;T;T
Eigen
Benign
-0.035
Eigen_PC
Benign
0.035
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.65
.;.;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.10
T;T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
0.0
N;N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.1
N;N;.
REVEL
Benign
0.073
Sift
Pathogenic
0.0
D;D;.
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.57
P;P;P
Vest4
0.28
MutPred
0.24
Gain of glycosylation at A367 (P = 0.0119);Gain of glycosylation at A367 (P = 0.0119);Gain of glycosylation at A367 (P = 0.0119);
MVP
0.26
MPC
0.38
ClinPred
0.25
T
GERP RS
3.7
Varity_R
0.18
gMVP
0.47

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

LitVar

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

Other links and lift over

dbSNP: rs539939023; hg19: chr9-34552178; API