Variant 18-48636622-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_014772.3(CTIF):c.189G>A(p.Ala63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00664 in 1,583,110 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0068 ( 53 hom. )

Consequence

CTIF
NM_014772.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.834

Variant links:

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]

CTIF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 18-48636622-G-A is Benign according to our data. Variant chr18-48636622-G-A is described in ClinVar as [Benign]. Clinvar id is 771922.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.834 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00678 (9703/1430782) while in subpopulation MID AF= 0.0434 (245/5642). AF 95% confidence interval is 0.039. There are 53 homozygotes in gnomad4_exome. There are 4876 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTIF	NM_014772.3 linkuse as main transcript	c.189G>A	p.Ala63=	synonymous_variant	3/12	ENST00000256413.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTIF	ENST00000256413.8 linkuse as main transcript	c.189G>A	p.Ala63=	synonymous_variant	3/12	1	NM_014772.3	A1	O43310-1

Frequencies

GnomAD3 genomes

AF:

0.00529

AC:

805

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00680

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00763

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00625

AC:

1372

AN:

219560

Hom.:

AF XY:

0.00660

AC XY:

788

AN XY:

119364

show subpopulations

Gnomad AFR exome

AF:

0.000949

Gnomad AMR exome

AF:

0.00655

Gnomad ASJ exome

AF:

0.00927

Gnomad EAS exome

AF:

0.000189

Gnomad SAS exome

AF:

0.00629

Gnomad FIN exome

AF:

0.00131

Gnomad NFE exome

AF:

0.00811

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.00678

AC:

9703

AN:

1430782

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

4876

AN XY:

710564

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00683

Gnomad4 ASJ exome

AF:

0.00983

Gnomad4 EAS exome

AF:

0.000210

Gnomad4 SAS exome

AF:

0.00578

Gnomad4 FIN exome

AF:

0.00256

Gnomad4 NFE exome

AF:

0.00712

Gnomad4 OTH exome

AF:

0.00781

GnomAD4 genome

AF:

0.00529

AC:

806

AN:

152328

Hom.:

Cov.:

AF XY:

0.00495

AC XY:

369

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00679

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00763

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.00688

Hom.:

Bravo

AF:

0.00552

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.5

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over