18-48619641-C-T

Variant summary

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

The NM_014772.3(CTIF):​c.76C>T​(p.Arg26Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000654 in 1,605,672 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 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

CTIF
NM_014772.3 missense

Scores

5
4
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67
Variant links:
Genes affected
CTIF (HGNC:23925): (cap binding complex dependent translation initiation factor) CTIF is a component of the CBP80 (NCBP1; MIM 600469)/CBP20 (NCBP2; MIM 605133) translation initiation complex that binds cotranscriptionally to the cap end of nascent mRNA. The CBP80/CBP20 complex is involved in a simultaneous editing and translation step that recognizes premature termination codons (PTCs) in mRNAs and directs PTC-containing mRNAs toward nonsense-mediated decay (NMD). On mRNAs without PTCs, the CBP80/CBP20 complex is replaced with cytoplasmic mRNA cap-binding proteins, including EIF4G (MIM 600495), and steady-state translation of the mRNAs resumes in the cytoplasm (Kim et al., 2009 [PubMed 19648179]).[supplied by OMIM, Dec 2009]

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=0.09885156).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CTIFNM_014772.3 linkc.76C>T p.Arg26Cys missense_variant Exon 2 of 12 ENST00000256413.8 NP_055587.1 O43310-1A0A024R259

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CTIFENST00000256413.8 linkc.76C>T p.Arg26Cys missense_variant Exon 2 of 12 1 NM_014772.3 ENSP00000256413.3 O43310-1

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152260
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000949
AC:
22
AN:
231726
Hom.:
0
AF XY:
0.000119
AC XY:
15
AN XY:
125576
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000918
Gnomad ASJ exome
AF:
0.00135
Gnomad EAS exome
AF:
0.0000575
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000383
Gnomad OTH exome
AF:
0.000177
GnomAD4 exome
AF:
0.0000688
AC:
100
AN:
1453412
Hom.:
0
Cov.:
30
AF XY:
0.0000706
AC XY:
51
AN XY:
722222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000685
Gnomad4 ASJ exome
AF:
0.00112
Gnomad4 EAS exome
AF:
0.000102
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.0000433
Gnomad4 OTH exome
AF:
0.000250
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152260
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000163
Hom.:
0
Bravo
AF:
0.0000604
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000495
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.76C>T (p.R26C) alteration is located in exon 3 (coding exon 1) of the CTIF gene. This alteration results from a C to T substitution at nucleotide position 76, causing the arginine (R) at amino acid position 26 to be replaced by a cysteine (C). 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
Pathogenic
0.88
BayesDel_addAF
Benign
-0.040
T
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.057
T;.;.;T;T;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.93
D
M_CAP
Uncertain
0.23
D
MetaRNN
Benign
0.099
T;T;T;T;T;T
MetaSVM
Benign
-0.42
T
MutationAssessor
Benign
0.0
N;N;.;.;.;.
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-2.3
N;N;.;.;.;.
REVEL
Benign
0.27
Sift
Pathogenic
0.0
D;D;.;.;.;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Polyphen
1.0
D;D;.;.;.;.
Vest4
0.88
MVP
0.37
MPC
0.77
ClinPred
0.26
T
GERP RS
4.2
Varity_R
0.30
gMVP
0.46

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: rs141259800; hg19: chr18-46146012; API