chr18-48790717-C-T

Variant names:

• chr18-48790717-C-T
• rs12455557
• NM_014772.3:c.1372-26504C>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.1372-26504C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,202 control chromosomes in the GnomAD database, including 1,842 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 0.15 (1842 hom., cov: 33)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.500
• Publications: 9 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTIF	NM_014772.3	c.1372-26504C>T		intron_variant	Intron 9 of 11	ENST00000256413.8	NP_055587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.1372-26504C>T		intron_variant	Intron 9 of 11	1	NM_014772.3	ENSP00000256413.3
CTIF	ENST00000382998.8	c.1378-26504C>T		intron_variant	Intron 10 of 12	1		ENSP00000372459.3
CTIF	ENST00000587860.1	n.1509-26504C>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22809 AN: 152082 Hom.: 1833 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.150 AC: 22839 AN: 152202 Hom.: 1842 Cov.: 33 AF XY: 0.153 AC XY: 11415 AN XY: 74412

African (AFR) AF: 0.130 AC: 5409 AN: 41534

American (AMR) AF: 0.211 AC: 3233 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3468

East Asian (EAS) AF: 0.250 AC: 1293 AN: 5166

South Asian (SAS) AF: 0.240 AC: 1155 AN: 4818

European-Finnish (FIN) AF: 0.128 AC: 1359 AN: 10604

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9376 AN: 67990

Other (OTH) AF: 0.178 AC: 376 AN: 2114

Alfa AF: 0.142 Hom.: 3571

Bravo AF: 0.154

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.90
PhyloP100		0.50
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: rs12455557; hg19: chr18-46317088;