chr18-48694870-T-C

Variant names:

• chr18-48694870-T-C
• rs8090378
• NM_014772.3:c.508-16749T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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]

LOC105372107 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.508-16749T>C		intron	N/A	NP_055587.1	O43310-1
	CTIF	NM_001142397.2		c.508-16749T>C		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.508-16749T>C		intron	N/A	ENSP00000256413.3	O43310-1
	CTIF	ENST00000382998.8	TSL:1	c.508-16749T>C		intron	N/A	ENSP00000372459.3	O43310-2
	CTIF	ENST00000865538.1		c.556-16749T>C		intron	N/A	ENSP00000535597.1

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

African (AFR) AF: 0.410 AC: 17010 AN: 41522

American (AMR) AF: 0.0628 AC: 962 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0744 AC: 258 AN: 3470

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5194

South Asian (SAS) AF: 0.0267 AC: 129 AN: 4828

European-Finnish (FIN) AF: 0.0841 AC: 893 AN: 10614

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0396 AC: 2694 AN: 68032

Other (OTH) AF: 0.0998 AC: 211 AN: 2114

Alfa AF: 0.118 Hom.: 338

Bravo AF: 0.157

Asia WGS AF: 0.0390 AC: 137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.38
DANN	Benign	0.43
PhyloP100		-1.8
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: rs8090378; hg19: chr18-46221241;