rs7227797

Variant names:

• chr18-48597300-A-G
• rs7227797
• NM_014772.3:c.-28-22238A>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.-28-22238A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,068 control chromosomes in the GnomAD database, including 13,230 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 0.39 (13230 hom., cov: 32)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTIF	NM_014772.3	c.-28-22238A>G		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.-28-22238A>G		intron_variant	Intron 1 of 11	1	NM_014772.3	ENSP00000256413.3

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59183 AN: 151950 Hom.: 13202 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.0944

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.390 AC: 59272 AN: 152068 Hom.: 13230 Cov.: 32 AF XY: 0.384 AC XY: 28559 AN XY: 74360

African (AFR) AF: 0.617 AC: 25603 AN: 41474

American (AMR) AF: 0.264 AC: 4036 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1168 AN: 3470

East Asian (EAS) AF: 0.0946 AC: 490 AN: 5180

South Asian (SAS) AF: 0.336 AC: 1621 AN: 4818

European-Finnish (FIN) AF: 0.309 AC: 3263 AN: 10572

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21902 AN: 67956

Other (OTH) AF: 0.354 AC: 749 AN: 2116

Alfa AF: 0.334 Hom.: 7291

Bravo AF: 0.394

Asia WGS AF: 0.219 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.2
DANN	Benign	0.53
PhyloP100		0.25
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: rs7227797; hg19: chr18-46123671;