chr18-48788013-G-T

Variant names:

• chr18-48788013-G-T
• rs11877669
• NM_014772.3:c.1371+26324G>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.1371+26324G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,004 control chromosomes in the GnomAD database, including 9,547 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 0.35 (9547 hom., cov: 32)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTIF	NM_014772.3	c.1371+26324G>T		intron_variant	Intron 9 of 11	ENST00000256413.8	NP_055587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.1371+26324G>T		intron_variant	Intron 9 of 11	1	NM_014772.3	ENSP00000256413.3
CTIF	ENST00000382998.8	c.1377+26324G>T		intron_variant	Intron 10 of 12	1		ENSP00000372459.3
CTIF	ENST00000587860.1	n.1508+26324G>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53280 AN: 151886 Hom.: 9546 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.351 AC: 53307 AN: 152004 Hom.: 9547 Cov.: 32 AF XY: 0.349 AC XY: 25901 AN XY: 74272

African (AFR) AF: 0.370 AC: 15319 AN: 41438

American (AMR) AF: 0.450 AC: 6872 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1047 AN: 3470

East Asian (EAS) AF: 0.213 AC: 1100 AN: 5170

South Asian (SAS) AF: 0.329 AC: 1583 AN: 4812

European-Finnish (FIN) AF: 0.315 AC: 3326 AN: 10572

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22946 AN: 67942

Other (OTH) AF: 0.357 AC: 755 AN: 2114

Alfa AF: 0.341 Hom.: 35869

Bravo AF: 0.366

Asia WGS AF: 0.262 AC: 915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.90
DANN	Benign	0.66
PhyloP100		-0.29
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: rs11877669; hg19: chr18-46314384;