chr18-48721052-G-A

Variant names:

• chr18-48721052-G-A
• rs11082695
• NM_014772.3:c.584+9357G>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.584+9357G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,182 control chromosomes in the GnomAD database, including 2,952 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 0.19 (2952 hom., cov: 32)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTIF	NM_014772.3	c.584+9357G>A		intron_variant	Intron 7 of 11	ENST00000256413.8	NP_055587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.584+9357G>A		intron_variant	Intron 7 of 11	1	NM_014772.3	ENSP00000256413.3
CTIF	ENST00000382998.8	c.584+9357G>A		intron_variant	Intron 8 of 12	1		ENSP00000372459.3
CTIF	ENST00000587769.1	n.236+9357G>A		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28736 AN: 152064 Hom.: 2949 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.189 AC: 28751 AN: 152182 Hom.: 2952 Cov.: 32 AF XY: 0.191 AC XY: 14194 AN XY: 74398

African (AFR) AF: 0.201 AC: 8359 AN: 41520

American (AMR) AF: 0.161 AC: 2470 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 796 AN: 3468

East Asian (EAS) AF: 0.154 AC: 795 AN: 5152

South Asian (SAS) AF: 0.368 AC: 1771 AN: 4818

European-Finnish (FIN) AF: 0.133 AC: 1411 AN: 10612

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12362 AN: 68006

Other (OTH) AF: 0.194 AC: 410 AN: 2108

Alfa AF: 0.195 Hom.: 1846

Bravo AF: 0.187

Asia WGS AF: 0.260 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.84
PhyloP100		-0.33
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: rs11082695; hg19: chr18-46247423;