18-48857414-T-C

Variant names:

• chr18-48857414-T-C
• rs937023
• NM_014772.3:c.1528-174T>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.1528-174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,130 control chromosomes in the GnomAD database, including 9,803 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 0.34 (9803 hom., cov: 33)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTIF	NM_014772.3	c.1528-174T>C		intron_variant	Intron 10 of 11	ENST00000256413.8	NP_055587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.1528-174T>C		intron_variant	Intron 10 of 11	1	NM_014772.3	ENSP00000256413.3
CTIF	ENST00000382998.8	c.1534-174T>C		intron_variant	Intron 11 of 12	1		ENSP00000372459.3
CTIF	ENST00000587860.1	n.1665-174T>C		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52175 AN: 152012 Hom.: 9791 Cov.: 33

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.343 AC: 52237 AN: 152130 Hom.: 9803 Cov.: 33 AF XY: 0.338 AC XY: 25160 AN XY: 74374

African (AFR) AF: 0.494 AC: 20492 AN: 41480

American (AMR) AF: 0.377 AC: 5759 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1401 AN: 3470

East Asian (EAS) AF: 0.232 AC: 1201 AN: 5174

South Asian (SAS) AF: 0.175 AC: 844 AN: 4822

European-Finnish (FIN) AF: 0.210 AC: 2225 AN: 10596

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19309 AN: 67982

Other (OTH) AF: 0.346 AC: 729 AN: 2108

Alfa AF: 0.310 Hom.: 24493

Bravo AF: 0.365

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.72
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs937023; hg19: chr18-46383785; COSMIC: COSV56491343; COSMIC: COSV56491343;