18-48548678-G-A

Variant names:

• chr18-48548678-G-A
• rs6507852
• NM_014772.3:c.-29+9366G>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.-29+9366G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,206 control chromosomes in the GnomAD database, including 39,357 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 0.70 (39357 hom., cov: 34)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 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.-29+9366G>A		intron	N/A	NP_055587.1
	CTIF	NM_001142397.2		c.-29+8847G>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.-29+9366G>A		intron	N/A	ENSP00000256413.3
	CTIF	ENST00000382998.8	TSL:1	c.-29+8847G>A		intron	N/A	ENSP00000372459.3
	CTIF	ENST00000587752.5	TSL:5	c.-29+8620G>A		intron	N/A	ENSP00000465405.2

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107238 AN: 152088 Hom.: 39349 Cov.: 34

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.721

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

GnomAD4 genome AF: 0.705 AC: 107281 AN: 152206 Hom.: 39357 Cov.: 34 AF XY: 0.709 AC XY: 52769 AN XY: 74430

African (AFR) AF: 0.487 AC: 20201 AN: 41500

American (AMR) AF: 0.766 AC: 11720 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2586 AN: 3472

East Asian (EAS) AF: 0.954 AC: 4942 AN: 5182

South Asian (SAS) AF: 0.656 AC: 3164 AN: 4824

European-Finnish (FIN) AF: 0.830 AC: 8801 AN: 10600

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53387 AN: 68012

Other (OTH) AF: 0.724 AC: 1527 AN: 2108

Alfa AF: 0.746 Hom.: 65247

Bravo AF: 0.697

Asia WGS AF: 0.801 AC: 2784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.7
DANN	Benign	0.72
PhyloP100		1.4
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: rs6507852; hg19: chr18-46075049;