Variant 9-34564715-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_147164.3(CNTFR):c.203T>C(p.Leu68Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.00013 ( 0 hom. )

Consequence

CNTFR
NM_147164.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.93

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]

CNTFR links:

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=0.08594972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTFR	NM_147164.3 linkuse as main transcript	c.203T>C	p.Leu68Pro	missense_variant	4/10	ENST00000378980.8	NP_671693.1	P26992

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CNTFR	ENST00000378980.8 linkuse as main transcript	c.203T>C	p.Leu68Pro	missense_variant	4/10	1	NM_147164.3	ENSP00000368265.3	P26992
CNTFR	ENST00000351266.8 linkuse as main transcript	c.203T>C	p.Leu68Pro	missense_variant	3/9	1		ENSP00000242338.4	P26992
CNTFR	ENST00000610543.4 linkuse as main transcript	c.203T>C	p.Leu68Pro	missense_variant	4/10	5		ENSP00000480451.1	P26992
CNTFR	ENST00000417345.2 linkuse as main transcript	c.203T>C	p.Leu68Pro	missense_variant	4/7	3		ENSP00000388082.1	Q5T8H6

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000139

AC:

AN:

251054

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135758

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:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000256

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000131

AC:

191

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000159

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000112

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000893

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2022

The c.203T>C (p.L68P) alteration is located in exon 4 (coding exon 2) of the CNTFR gene. This alteration results from a T to C substitution at nucleotide position 203, causing the leucine (L) at amino acid position 68 to be replaced by a proline (P). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

T;T;T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.062

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.67

.;.;T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.086

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;N;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.37

N;N;.;N

REVEL

Benign

0.12

Sift

Benign

0.29

T;T;.;T

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.041

B;B;B;.

Vest4

0.54

MVP

0.24

MPC

0.74

ClinPred

0.075

GERP RS

4.1

Varity_R

0.14

gMVP

0.85

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over