rs7233521

Positions:

• chr18-48693362-G-A
• chr18-48693362-G-C

Variant summary

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

The ENST00000256413.8(CTIF):​c.508-18257G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,196 control chromosomes in the GnomAD database, including 2,376 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 0.15 (2376 hom., cov: 32)
• Consequence: CTIF ENST00000256413.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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]

LOC105372107 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTIF	NM_014772.3	c.508-18257G>A		intron_variant		ENST00000256413.8	NP_055587.1
LOC105372107	XR_007066460.1	n.11064C>T		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.508-18257G>A		intron_variant		1	NM_014772.3	ENSP00000256413	A1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22095 AN: 152078 Hom.: 2377 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.145 AC: 22114 AN: 152196 Hom.: 2376 Cov.: 32 AF XY: 0.142 AC XY: 10536 AN XY: 74420

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0176

Gnomad4 FIN AF: 0.0755

Gnomad4 NFE AF: 0.0929

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0971 Hom.: 1627

Bravo AF: 0.155

Asia WGS AF: 0.0300 AC: 104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.19
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs7233521; hg19: chr18-46219733;