chr18-48550407-C-A

Position:

• chr18-48550407-C-A

Variant summary

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

The NM_014772.3(CTIF):​c.-29+11095C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,164 control chromosomes in the GnomAD database, including 45,113 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 0.77 (45113 hom., cov: 33)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTIF	NM_014772.3	c.-29+11095C>A		intron_variant		ENST00000256413.8	NP_055587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.-29+11095C>A		intron_variant		1	NM_014772.3	ENSP00000256413	A1

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116670 AN: 152046 Hom.: 45079 Cov.: 33

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.767 AC: 116760 AN: 152164 Hom.: 45113 Cov.: 33 AF XY: 0.769 AC XY: 57220 AN XY: 74392

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.786

Gnomad4 OTH AF: 0.761

Alfa AF: 0.779 Hom.: 11498

Bravo AF: 0.767

Asia WGS AF: 0.827 AC: 2876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.41

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: rs9952398; hg19: chr18-46076778;