rs6507852

Positions:

• chr18-48548678-G-A
• chr18-48548678-G-C

Variant summary

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

The NM_014772.3(CTIF):​c.-29+9366G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,206 control chromosomes in the GnomAD database, including 39,357 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 0.70 (39357 hom., cov: 34)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTIF	NM_014772.3	c.-29+9366G>A		intron_variant		ENST00000256413.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTIF	ENST00000256413.8	c.-29+9366G>A		intron_variant		1	NM_014772.3	A1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107238 AN: 152088 Hom.: 39349 Cov.: 34

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.721

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

GnomAD4 genome AF: 0.705 AC: 107281 AN: 152206 Hom.: 39357 Cov.: 34 AF XY: 0.709 AC XY: 52769 AN XY: 74430

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.954

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.724

Alfa AF: 0.721 Hom.: 7688

Bravo AF: 0.697

Asia WGS AF: 0.801 AC: 2784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.7
DANN	Benign	0.72

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: rs6507852; hg19: chr18-46075049;