rs873816

Variant names:

• chr18-48574703-C-T
• rs873816
• NM_014772.3:c.-29+35391C>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.-29+35391C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,122 control chromosomes in the GnomAD database, including 46,202 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 0.77 (46202 hom., cov: 32)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTIF	NM_014772.3	c.-29+35391C>T		intron_variant	Intron 1 of 11	ENST00000256413.8	NP_055587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.-29+35391C>T		intron_variant	Intron 1 of 11	1	NM_014772.3	ENSP00000256413.3

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117239 AN: 152004 Hom.: 46187 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.771 AC: 117299 AN: 152122 Hom.: 46202 Cov.: 32 AF XY: 0.771 AC XY: 57351 AN XY: 74372

African (AFR) AF: 0.597 AC: 24721 AN: 41432

American (AMR) AF: 0.841 AC: 12864 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2510 AN: 3470

East Asian (EAS) AF: 0.963 AC: 4982 AN: 5174

South Asian (SAS) AF: 0.707 AC: 3410 AN: 4826

European-Finnish (FIN) AF: 0.831 AC: 8810 AN: 10600

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57352 AN: 68012

Other (OTH) AF: 0.782 AC: 1654 AN: 2114

Alfa AF: 0.821 Hom.: 102723

Bravo AF: 0.767

Asia WGS AF: 0.816 AC: 2840 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	0.25
DANN	Benign	0.61
PhyloP100		-1.0
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: rs873816; hg19: chr18-46101074;