rs9947954

Positions:

• chr18-48714340-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014772.3(CTIF):​c.584+2645A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,962 control chromosomes in the GnomAD database, including 22,598 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 0.52 (22598 hom., cov: 32)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397

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

Verdict is Benign. Variant got -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 = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTIF	NM_014772.3	c.584+2645A>C		intron_variant		ENST00000256413.8	NP_055587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.584+2645A>C		intron_variant		1	NM_014772.3	ENSP00000256413	A1
CTIF	ENST00000382998.8	c.584+2645A>C		intron_variant		1		ENSP00000372459	P3
CTIF	ENST00000587769.1	n.236+2645A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78795 AN: 151844 Hom.: 22553 Cov.: 32

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.519 AC: 78888 AN: 151962 Hom.: 22598 Cov.: 32 AF XY: 0.514 AC XY: 38150 AN XY: 74272

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.498

Alfa AF: 0.454 Hom.: 10237

Bravo AF: 0.528

Asia WGS AF: 0.400 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.1
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs9947954; hg19: chr18-46240711;