18-48550603-G-T

Variant names:

• chr18-48550603-G-T
• rs12456253
• NM_014772.3:c.-29+11291G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014772.3(CTIF):​c.-29+11291G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,030 control chromosomes in the GnomAD database, including 30,858 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (30858 hom., cov: 31)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTIF	NM_014772.3	MANE Select	c.-29+11291G>T		intron	N/A	NP_055587.1
	CTIF	NM_001142397.2		c.-29+10772G>T		intron	N/A	NP_001135869.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTIF	ENST00000256413.8	TSL:1 MANE Select	c.-29+11291G>T		intron	N/A	ENSP00000256413.3
	CTIF	ENST00000382998.8	TSL:1	c.-29+10772G>T		intron	N/A	ENSP00000372459.3
	CTIF	ENST00000587752.5	TSL:5	c.-29+10545G>T		intron	N/A	ENSP00000465405.2

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94451 AN: 151910 Hom.: 30850 Cov.: 31

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.622 AC: 94491 AN: 152030 Hom.: 30858 Cov.: 31 AF XY: 0.625 AC XY: 46422 AN XY: 74298

African (AFR) AF: 0.415 AC: 17219 AN: 41450

American (AMR) AF: 0.694 AC: 10608 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2041 AN: 3470

East Asian (EAS) AF: 0.924 AC: 4779 AN: 5170

South Asian (SAS) AF: 0.557 AC: 2683 AN: 4818

European-Finnish (FIN) AF: 0.728 AC: 7700 AN: 10580

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47269 AN: 67938

Other (OTH) AF: 0.632 AC: 1332 AN: 2108

Alfa AF: 0.634 Hom.: 6393

Bravo AF: 0.616

Asia WGS AF: 0.718 AC: 2499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.070
DANN	Benign	0.74
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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: rs12456253; hg19: chr18-46076974;