chr18-48664499-C-G

Variant names:

• chr18-48664499-C-G
• rs1443832008
• NM_014772.3:c.379C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014772.3(CTIF):​c.379C>G​(p.Arg127Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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: 0.187
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15301442).

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.379C>G	p.Arg127Gly	missense	Exon 5 of 12	NP_055587.1	O43310-1
	CTIF	NM_001142397.2		c.379C>G	p.Arg127Gly	missense	Exon 6 of 13	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.379C>G	p.Arg127Gly	missense	Exon 5 of 12	ENSP00000256413.3	O43310-1
	CTIF	ENST00000382998.8	TSL:1	c.379C>G	p.Arg127Gly	missense	Exon 6 of 13	ENSP00000372459.3	O43310-2
	CTIF	ENST00000865538.1		c.427C>G	p.Arg143Gly	missense	Exon 7 of 14	ENSP00000535597.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.16	N
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.19
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.081
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.14	T
Polyphen		0.0040	B
Vest4		0.88
MutPred		0.33		Loss of stability (P = 0.0498)
MVP		0.24
MPC		0.20
ClinPred		0.47	T
GERP RS		0.49
Varity_R		0.18
gMVP		0.42

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

Other links and lift over

dbSNP: rs1443832008; hg19: chr18-46190870;