chr18-48793314-G-A

Variant names:

• chr18-48793314-G-A
• rs4583322
• NM_014772.3:c.1372-23907G>A

Variant summary

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

The NM_014772.3(CTIF):​c.1372-23907G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,054 control chromosomes in the GnomAD database, including 16,418 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 0.44 (16418 hom., cov: 32)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTIF	NM_014772.3	MANE Select	c.1372-23907G>A		intron	N/A	NP_055587.1
	CTIF	NM_001142397.2		c.1378-23907G>A		intron	N/A	NP_001135869.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTIF	ENST00000256413.8	TSL:1 MANE Select	c.1372-23907G>A		intron	N/A	ENSP00000256413.3
	CTIF	ENST00000382998.8	TSL:1	c.1378-23907G>A		intron	N/A	ENSP00000372459.3
	CTIF	ENST00000587860.1	TSL:2	n.1509-23907G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67060 AN: 151936 Hom.: 16374 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.442 AC: 67175 AN: 152054 Hom.: 16418 Cov.: 32 AF XY: 0.439 AC XY: 32606 AN XY: 74326

African (AFR) AF: 0.668 AC: 27674 AN: 41428

American (AMR) AF: 0.413 AC: 6314 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1131 AN: 3472

East Asian (EAS) AF: 0.301 AC: 1552 AN: 5160

South Asian (SAS) AF: 0.337 AC: 1622 AN: 4816

European-Finnish (FIN) AF: 0.347 AC: 3676 AN: 10586

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23909 AN: 67986

Other (OTH) AF: 0.413 AC: 873 AN: 2112

Alfa AF: 0.375 Hom.: 49641

Bravo AF: 0.456

Asia WGS AF: 0.335 AC: 1163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.52
PhyloP100		1.1
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: rs4583322; hg19: chr18-46319685;