chr18-48701073-C-G

Variant names:

• chr18-48701073-C-G
• rs16949825
• NM_014772.3:c.508-10546C>G

Variant summary

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

The NM_014772.3(CTIF):​c.508-10546C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,188 control chromosomes in the GnomAD database, including 1,853 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 0.14 (1853 hom., cov: 33)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 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.508-10546C>G		intron	N/A	NP_055587.1	O43310-1
	CTIF	NM_001142397.2		c.508-10546C>G		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.508-10546C>G		intron	N/A	ENSP00000256413.3	O43310-1
	CTIF	ENST00000382998.8	TSL:1	c.508-10546C>G		intron	N/A	ENSP00000372459.3	O43310-2
	CTIF	ENST00000865538.1		c.556-10546C>G		intron	N/A	ENSP00000535597.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20710 AN: 152070 Hom.: 1855 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0959

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.136 AC: 20727 AN: 152188 Hom.: 1853 Cov.: 33 AF XY: 0.133 AC XY: 9916 AN XY: 74404

African (AFR) AF: 0.253 AC: 10478 AN: 41476

American (AMR) AF: 0.118 AC: 1799 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 588 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0212 AC: 102 AN: 4820

European-Finnish (FIN) AF: 0.0815 AC: 864 AN: 10598

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0959 AC: 6524 AN: 68022

Other (OTH) AF: 0.140 AC: 295 AN: 2114

Alfa AF: 0.119 Hom.: 179

Bravo AF: 0.147

Asia WGS AF: 0.0280 AC: 98 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.21
DANN	Benign	0.44
PhyloP100		-0.097
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: rs16949825; hg19: chr18-46227444;