rs8091955

Positions:

• chr18-48832536-G-A
• chr18-48832536-G-T

Variant summary

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

The NM_014772.3(CTIF):​c.1527+15160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,074 control chromosomes in the GnomAD database, including 22,633 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 0.52 (22633 hom., cov: 32)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349

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]

LOC105372105 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTIF	NM_014772.3	c.1527+15160G>A		intron_variant		ENST00000256413.8	NP_055587.1
LOC105372105	XR_007066459.1	n.2854C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.1527+15160G>A		intron_variant		1	NM_014772.3	ENSP00000256413	A1
CTIF	ENST00000382998.8	c.1533+15160G>A		intron_variant		1		ENSP00000372459	P3
	ENST00000590649.1	n.79+2156C>T		intron_variant, non_coding_transcript_variant		3
CTIF	ENST00000587860.1	n.1664+15160G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79764 AN: 151956 Hom.: 22624 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.525 AC: 79803 AN: 152074 Hom.: 22633 Cov.: 32 AF XY: 0.532 AC XY: 39567 AN XY: 74340

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.968

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.562

Gnomad4 OTH AF: 0.561

Alfa AF: 0.571 Hom.: 37009

Bravo AF: 0.527

Asia WGS AF: 0.814 AC: 2828 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	1.1
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: rs8091955; hg19: chr18-46358907;