chr18-48811490-A-G

Position:

• chr18-48811490-A-G

Variant summary

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

The NM_014772.3(CTIF):​c.1372-5731A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,172 control chromosomes in the GnomAD database, including 1,534 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 0.14 (1534 hom., cov: 32)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTIF	NM_014772.3	c.1372-5731A>G		intron_variant		ENST00000256413.8	NP_055587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.1372-5731A>G		intron_variant		1	NM_014772.3	ENSP00000256413	A1
CTIF	ENST00000382998.8	c.1378-5731A>G		intron_variant		1		ENSP00000372459	P3
CTIF	ENST00000587860.1	n.1509-5731A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20989 AN: 152054 Hom.: 1530 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0897

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.138 AC: 21013 AN: 152172 Hom.: 1534 Cov.: 32 AF XY: 0.137 AC XY: 10206 AN XY: 74398

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0906

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.140

Alfa AF: 0.130 Hom.: 908

Bravo AF: 0.142

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.72

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: rs12959910; hg19: chr18-46337861;