rs12606093

chr18-48550924-C-Achr18-48550924-C-G

Variant summary

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

The NM_014772.3(CTIF):c.-29+11612C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,916 control chromosomes in the GnomAD database, including 30,604 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 (30604 hom., cov: 31)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTIF	NM_014772.3	c.-29+11612C>A		intron_variant		ENST00000256413.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTIF	ENST00000256413.8	c.-29+11612C>A		intron_variant		1	NM_014772.3	A1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93853 AN: 151798 Hom.: 30600 Cov.: 31

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.618 AC: 93887 AN: 151916 Hom.: 30604 Cov.: 31 AF XY: 0.621 AC XY: 46135 AN XY: 74256

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.924

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.630

Alfa AF: 0.677 Hom.: 35151

Bravo AF: 0.612

Asia WGS AF: 0.718 AC: 2499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.3
Dann	Benign	0.81

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: rs12606093; hg19: chr18-46077295;