chr18-48847705-T-C

Variant names:

• chr18-48847705-T-C
• rs11661879
• NM_014772.3:c.1528-9883T>C

Variant summary

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

The NM_001142397.2(CTIF):​c.1534-9883T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,104 control chromosomes in the GnomAD database, including 16,322 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 0.42 (16322 hom., cov: 33)
• Consequence: CTIF NM_001142397.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142397.2. 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.1528-9883T>C		intron	N/A	NP_055587.1
	CTIF	NM_001142397.2		c.1534-9883T>C		intron	N/A	NP_001135869.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTIF	ENST00000256413.8	TSL:1 MANE Select	c.1528-9883T>C		intron	N/A	ENSP00000256413.3
	CTIF	ENST00000382998.8	TSL:1	c.1534-9883T>C		intron	N/A	ENSP00000372459.3
	CTIF	ENST00000865538.1		c.1582-9883T>C		intron	N/A	ENSP00000535597.1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64070 AN: 151986 Hom.: 16293 Cov.: 33

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.422 AC: 64148 AN: 152104 Hom.: 16322 Cov.: 33 AF XY: 0.418 AC XY: 31047 AN XY: 74352

African (AFR) AF: 0.720 AC: 29851 AN: 41480

American (AMR) AF: 0.400 AC: 6120 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1335 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1018 AN: 5186

South Asian (SAS) AF: 0.344 AC: 1657 AN: 4812

European-Finnish (FIN) AF: 0.261 AC: 2759 AN: 10580

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20279 AN: 67968

Other (OTH) AF: 0.399 AC: 841 AN: 2110

Alfa AF: 0.386 Hom.: 4710

Bravo AF: 0.445

Asia WGS AF: 0.299 AC: 1042 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	0.83
DANN	Benign	0.58
PhyloP100		-0.35
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: rs11661879; hg19: chr18-46374076;