18-48694870-T-C

Position:

• chr18-48694870-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.508-16749T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,288 control chromosomes in the GnomAD database, including 3,664 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 (3664 hom., cov: 33)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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]

LOC105372107 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTIF	NM_014772.3	c.508-16749T>C		intron_variant		ENST00000256413.8	NP_055587.1
LOC105372107	XR_007066460.1	n.9556A>G		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.508-16749T>C		intron_variant		1	NM_014772.3	ENSP00000256413	A1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22118 AN: 152170 Hom.: 3643 Cov.: 33

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.000960

Gnomad SAS AF: 0.0267

Gnomad FIN AF: 0.0841

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0396

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.146 AC: 22192 AN: 152288 Hom.: 3664 Cov.: 33 AF XY: 0.143 AC XY: 10627 AN XY: 74474

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.0744

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0267

Gnomad4 FIN AF: 0.0841

Gnomad4 NFE AF: 0.0396

Gnomad4 OTH AF: 0.0998

Alfa AF: 0.107 Hom.: 280

Bravo AF: 0.157

Asia WGS AF: 0.0390 AC: 137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.38
DANN	Benign	0.43

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: rs8090378; hg19: chr18-46221241;