rs12606093

Variant names:

• chr18-48550924-C-A
• rs12606093
• NM_014772.3:c.-29+11612C>A

Your query was ambiguous. Multiple possible variants found:

• chr18-48550924-C-A
• chr18-48550924-C-G

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+11612C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,916 control chromosomes in the GnomAD database, including 30,604 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 0.62 (30604 hom., cov: 31)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTIF	NM_014772.3	c.-29+11612C>A		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.-29+11612C>A		intron_variant	Intron 1 of 11	1	NM_014772.3	ENSP00000256413.3

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93853 AN: 151798 Hom.: 30600 Cov.: 31

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.618 AC: 93887 AN: 151916 Hom.: 30604 Cov.: 31 AF XY: 0.621 AC XY: 46135 AN XY: 74256

African (AFR) AF: 0.403 AC: 16660 AN: 41366

American (AMR) AF: 0.692 AC: 10563 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2036 AN: 3466

East Asian (EAS) AF: 0.924 AC: 4783 AN: 5176

South Asian (SAS) AF: 0.558 AC: 2687 AN: 4816

European-Finnish (FIN) AF: 0.728 AC: 7683 AN: 10552

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47288 AN: 67960

Other (OTH) AF: 0.630 AC: 1328 AN: 2108

Alfa AF: 0.666 Hom.: 43395

Bravo AF: 0.612

Asia WGS AF: 0.718 AC: 2499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.81
PhyloP100		0.18
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: rs12606093; hg19: chr18-46077295;