rs7227892

Variant names:

• chr18-48810331-A-T
• rs7227892
• NM_014772.3:c.1372-6890A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014772.3(CTIF):​c.1372-6890A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,938 control chromosomes in the GnomAD database, including 8,650 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 0.32 (8650 hom., cov: 33)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTIF	NM_014772.3	c.1372-6890A>T		intron_variant	Intron 9 of 11	ENST00000256413.8	NP_055587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.1372-6890A>T		intron_variant	Intron 9 of 11	1	NM_014772.3	ENSP00000256413.3
CTIF	ENST00000382998.8	c.1378-6890A>T		intron_variant	Intron 10 of 12	1		ENSP00000372459.3
CTIF	ENST00000587860.1	n.1509-6890A>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49187 AN: 151820 Hom.: 8638 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0853

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.324 AC: 49246 AN: 151938 Hom.: 8650 Cov.: 33 AF XY: 0.322 AC XY: 23941 AN XY: 74240

African (AFR) AF: 0.433 AC: 17975 AN: 41474

American (AMR) AF: 0.419 AC: 6399 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3468

East Asian (EAS) AF: 0.0857 AC: 445 AN: 5192

South Asian (SAS) AF: 0.229 AC: 1102 AN: 4814

European-Finnish (FIN) AF: 0.281 AC: 2963 AN: 10536

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18567 AN: 67852

Other (OTH) AF: 0.304 AC: 641 AN: 2108

Alfa AF: 0.319 Hom.: 1040

Bravo AF: 0.339

Asia WGS AF: 0.184 AC: 637 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.89
DANN	Benign	0.78
PhyloP100		-0.19
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: rs7227892; hg19: chr18-46336702;