rs16949646

Variant names:

• chr18-48611704-C-G
• rs16949646
• NM_014772.3:c.-28-7834C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-48611704-C-G
• chr18-48611704-C-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.-28-7834C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,100 control chromosomes in the GnomAD database, including 16,976 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 0.43 (16976 hom., cov: 33)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTIF	NM_014772.3	c.-28-7834C>G		intron_variant	Intron 1 of 11	ENST00000256413.8	NP_055587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.-28-7834C>G		intron_variant	Intron 1 of 11	1	NM_014772.3	ENSP00000256413.3

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65707 AN: 151982 Hom.: 16940 Cov.: 33

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.433 AC: 65803 AN: 152100 Hom.: 16976 Cov.: 33 AF XY: 0.429 AC XY: 31878 AN XY: 74324

African (AFR) AF: 0.729 AC: 30248 AN: 41502

American (AMR) AF: 0.278 AC: 4242 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1302 AN: 3472

East Asian (EAS) AF: 0.124 AC: 642 AN: 5180

South Asian (SAS) AF: 0.461 AC: 2219 AN: 4816

European-Finnish (FIN) AF: 0.334 AC: 3524 AN: 10556

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22282 AN: 67986

Other (OTH) AF: 0.413 AC: 870 AN: 2108

Alfa AF: 0.217 Hom.: 470

Bravo AF: 0.435

Asia WGS AF: 0.300 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.52
PhyloP100		0.58
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: rs16949646; hg19: chr18-46138075;