18-48594569-C-T

Position:

• chr18-48594569-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014772.3(CTIF):​c.-28-24969C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,008 control chromosomes in the GnomAD database, including 4,028 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 0.23 (4028 hom., cov: 31)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTIF	NM_014772.3	c.-28-24969C>T		intron_variant		ENST00000256413.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTIF	ENST00000256413.8	c.-28-24969C>T		intron_variant		1	NM_014772.3	A1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34583 AN: 151888 Hom.: 4026 Cov.: 31

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.0679

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.228 AC: 34599 AN: 152008 Hom.: 4028 Cov.: 31 AF XY: 0.227 AC XY: 16834 AN XY: 74306

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.0681

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.220

Alfa AF: 0.220 Hom.: 3162

Bravo AF: 0.222

Asia WGS AF: 0.139 AC: 481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.67
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs2337069; hg19: chr18-46120940;