chr18-48571956-G-A

Variant names:

• chr18-48571956-G-A
• rs4939781
• NM_014772.3:c.-29+32644G>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.-29+32644G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,110 control chromosomes in the GnomAD database, including 35,078 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 0.64 (35078 hom., cov: 32)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014772.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTIF	NM_014772.3	MANE Select	c.-29+32644G>A		intron	N/A	NP_055587.1
	CTIF	NM_001142397.2		c.-29+32125G>A		intron	N/A	NP_001135869.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTIF	ENST00000256413.8	TSL:1 MANE Select	c.-29+32644G>A		intron	N/A	ENSP00000256413.3
	CTIF	ENST00000382998.8	TSL:1	c.-29+32125G>A		intron	N/A	ENSP00000372459.3
	CTIF	ENST00000587752.5	TSL:5	c.-29+31898G>A		intron	N/A	ENSP00000465405.2

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97396 AN: 151992 Hom.: 35080 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.640 AC: 97403 AN: 152110 Hom.: 35078 Cov.: 32 AF XY: 0.644 AC XY: 47853 AN XY: 74358

African (AFR) AF: 0.286 AC: 11850 AN: 41480

American (AMR) AF: 0.740 AC: 11315 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2245 AN: 3466

East Asian (EAS) AF: 0.921 AC: 4761 AN: 5168

South Asian (SAS) AF: 0.604 AC: 2912 AN: 4822

European-Finnish (FIN) AF: 0.807 AC: 8543 AN: 10592

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53477 AN: 67982

Other (OTH) AF: 0.662 AC: 1397 AN: 2110

Alfa AF: 0.748 Hom.: 71521

Bravo AF: 0.623

Asia WGS AF: 0.729 AC: 2535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.79
PhyloP100		0.043
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: rs4939781; hg19: chr18-46098327;