18-48714646-C-T

Variant names:

• chr18-48714646-C-T
• rs11662494
• NM_014772.3:c.584+2951C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014772.3(CTIF):​c.584+2951C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,202 control chromosomes in the GnomAD database, including 2,547 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 0.17 (2547 hom., cov: 33)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014772.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTIF	NM_014772.3	MANE Select	c.584+2951C>T		intron	N/A	NP_055587.1	O43310-1
	CTIF	NM_001142397.2		c.584+2951C>T		intron	N/A	NP_001135869.1	O43310-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTIF	ENST00000256413.8	TSL:1 MANE Select	c.584+2951C>T		intron	N/A	ENSP00000256413.3	O43310-1
	CTIF	ENST00000382998.8	TSL:1	c.584+2951C>T		intron	N/A	ENSP00000372459.3	O43310-2
	CTIF	ENST00000865538.1		c.632+2951C>T		intron	N/A	ENSP00000535597.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26435 AN: 152084 Hom.: 2541 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.174 AC: 26447 AN: 152202 Hom.: 2547 Cov.: 33 AF XY: 0.175 AC XY: 13038 AN XY: 74416

African (AFR) AF: 0.182 AC: 7562 AN: 41516

American (AMR) AF: 0.150 AC: 2286 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 695 AN: 3468

East Asian (EAS) AF: 0.141 AC: 731 AN: 5182

South Asian (SAS) AF: 0.369 AC: 1775 AN: 4816

European-Finnish (FIN) AF: 0.125 AC: 1325 AN: 10606

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11334 AN: 68006

Other (OTH) AF: 0.176 AC: 373 AN: 2114

Alfa AF: 0.173 Hom.: 5386

Bravo AF: 0.172

Asia WGS AF: 0.257 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.66
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11662494; hg19: chr18-46241017;