rs9952724

Variant names:

• chr18-48726444-A-C
• rs9952724
• NM_014772.3:c.584+14749A>C

Your query was ambiguous. Multiple possible variants found:

• chr18-48726444-A-C
• chr18-48726444-A-T

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+14749A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,046 control chromosomes in the GnomAD database, including 7,351 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 0.29 (7351 hom., cov: 32)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTIF	NM_014772.3	c.584+14749A>C		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+14749A>C		intron_variant	Intron 7 of 11	1	NM_014772.3	ENSP00000256413.3
CTIF	ENST00000382998.8	c.584+14749A>C		intron_variant	Intron 8 of 12	1		ENSP00000372459.3
CTIF	ENST00000587769.1	n.236+14749A>C		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44105 AN: 151926 Hom.: 7340 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.0494

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.290 AC: 44158 AN: 152046 Hom.: 7351 Cov.: 32 AF XY: 0.286 AC XY: 21269 AN XY: 74326

African (AFR) AF: 0.452 AC: 18726 AN: 41434

American (AMR) AF: 0.208 AC: 3172 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1168 AN: 3468

East Asian (EAS) AF: 0.0493 AC: 255 AN: 5174

South Asian (SAS) AF: 0.124 AC: 600 AN: 4822

European-Finnish (FIN) AF: 0.276 AC: 2917 AN: 10576

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16482 AN: 67968

Other (OTH) AF: 0.257 AC: 543 AN: 2114

Alfa AF: 0.244 Hom.: 8403

Bravo AF: 0.294

Asia WGS AF: 0.111 AC: 385 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.082
DANN	Benign	0.71
PhyloP100		-1.5
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: rs9952724; hg19: chr18-46252815;