chr18-48857702-A-G

Position:

• chr18-48857702-A-G

Variant summary

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

The NM_014772.3(CTIF):​c.1581+61A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,503,380 control chromosomes in the GnomAD database, including 150,681 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 0.46 (16797 hom., cov: 33)
  • Exomes 𝑓: 0.44 (133884 hom.)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTIF	NM_014772.3	c.1581+61A>G		intron_variant		ENST00000256413.8	NP_055587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.1581+61A>G		intron_variant		1	NM_014772.3	ENSP00000256413	A1
CTIF	ENST00000382998.8	c.1587+61A>G		intron_variant		1		ENSP00000372459	P3
CTIF	ENST00000587860.1	n.1718+61A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70202 AN: 151880 Hom.: 16779 Cov.: 33

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.438 AC: 592452 AN: 1351380 Hom.: 133884 AF XY: 0.434 AC XY: 290684 AN XY: 670152

Gnomad4 AFR exome AF: 0.539

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.529

Gnomad4 EAS exome AF: 0.216

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.456

Gnomad4 OTH exome AF: 0.446

GnomAD4 genome AF: 0.462 AC: 70266 AN: 152000 Hom.: 16797 Cov.: 33 AF XY: 0.454 AC XY: 33710 AN XY: 74302

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.494

Alfa AF: 0.466 Hom.: 25032

Bravo AF: 0.482

Asia WGS AF: 0.230 AC: 800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.29
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs937021; hg19: chr18-46384073; COSMIC: COSV56481295; COSMIC: COSV56481295;