18-48695996-G-A

Variant names:

• chr18-48695996-G-A
• rs16949816
• NM_014772.3:c.508-15623G>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.508-15623G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0941 in 152,252 control chromosomes in the GnomAD database, including 1,896 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 0.094 (1896 hom., cov: 33)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541
• Publications: 0 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 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.508-15623G>A		intron	N/A	NP_055587.1
	CTIF	NM_001142397.2		c.508-15623G>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.508-15623G>A		intron	N/A	ENSP00000256413.3
	CTIF	ENST00000382998.8	TSL:1	c.508-15623G>A		intron	N/A	ENSP00000372459.3
	CTIF	ENST00000587752.5	TSL:5	c.508-15623G>A		intron	N/A	ENSP00000465405.2

Frequencies

GnomAD3 genomes AF: 0.0940 AC: 14307 AN: 152134 Hom.: 1894 Cov.: 33

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00641

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.0683

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

GnomAD4 genome AF: 0.0941 AC: 14330 AN: 152252 Hom.: 1896 Cov.: 33 AF XY: 0.0914 AC XY: 6808 AN XY: 74454

African (AFR) AF: 0.298 AC: 12373 AN: 41508

American (AMR) AF: 0.0446 AC: 682 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0680 AC: 236 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00663 AC: 32 AN: 4830

European-Finnish (FIN) AF: 0.0106 AC: 113 AN: 10626

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0108 AC: 732 AN: 68004

Other (OTH) AF: 0.0676 AC: 143 AN: 2116

Alfa AF: 0.0247 Hom.: 469

Bravo AF: 0.106

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.66
PhyloP100		0.54
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: rs16949816; hg19: chr18-46222367;