18-48674597-T-C

Position:

• chr18-48674597-T-C

Variant summary

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

The NM_014772.3(CTIF):​c.507+3853T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 152,254 control chromosomes in the GnomAD database, including 587 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 0.082 (587 hom., cov: 33)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTIF	NM_014772.3	c.507+3853T>C		intron_variant		ENST00000256413.8
LOC105372107	XR_007066460.1	n.12922-921A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTIF	ENST00000256413.8	c.507+3853T>C		intron_variant		1	NM_014772.3	A1
	ENST00000589818.1	n.364-921A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0821 AC: 12493 AN: 152136 Hom.: 586 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0936

Gnomad AMR AF: 0.0579

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.0623

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0652

Gnomad OTH AF: 0.0798

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

GnomAD4 genome AF: 0.0821 AC: 12503 AN: 152254 Hom.: 587 Cov.: 33 AF XY: 0.0822 AC XY: 6123 AN XY: 74464

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0578

Gnomad4 ASJ AF: 0.0787

Gnomad4 EAS AF: 0.0150

Gnomad4 SAS AF: 0.0624

Gnomad4 FIN AF: 0.0757

Gnomad4 NFE AF: 0.0652

Gnomad4 OTH AF: 0.0794

Alfa AF: 0.0668 Hom.: 518

Bravo AF: 0.0838

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.71

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: rs8085434; hg19: chr18-46200968;