18-48664499-CGC-GGA

Variant names:

• chr18-48664499-CGC-GGA
• NM_014772.3:c.379_381delCGCinsGGA
• CTIF p.Arg127Gly

Variant summary

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

The NM_014772.3(CTIF):​c.379_381delCGCinsGGA​(p.Arg127Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R127C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTIF NM_014772.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.97
• Publications: 0 publications found

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]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014772.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTIF	NM_014772.3	MANE Select	c.379_381delCGCinsGGA	p.Arg127Gly	missense	N/A	NP_055587.1	O43310-1
	CTIF	NM_001142397.2		c.379_381delCGCinsGGA	p.Arg127Gly	missense	N/A	NP_001135869.1	O43310-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTIF	ENST00000256413.8	TSL:1 MANE Select	c.379_381delCGCinsGGA	p.Arg127Gly	missense	N/A	ENSP00000256413.3	O43310-1
	CTIF	ENST00000382998.8	TSL:1	c.379_381delCGCinsGGA	p.Arg127Gly	missense	N/A	ENSP00000372459.3	O43310-2
	CTIF	ENST00000865538.1		c.427_429delCGCinsGGA	p.Arg143Gly	missense	N/A	ENSP00000535597.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr18-46190870;