Variant 8-38030610-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_004095.4(EIF4EBP1):c.37C>T(p.Arg13Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 1,510,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

EIF4EBP1
NM_004095.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

Variant links:

Genes affected

EIF4EBP1 (HGNC:3288): (eukaryotic translation initiation factor 4E binding protein 1) This gene encodes one member of a family of translation repressor proteins. The protein directly interacts with eukaryotic translation initiation factor 4E (eIF4E), which is a limiting component of the multisubunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. Interaction of this protein with eIF4E inhibits complex assembly and represses translation. This protein is phosphorylated in response to various signals including UV irradiation and insulin signaling, resulting in its dissociation from eIF4E and activation of mRNA translation. [provided by RefSeq, Jul 2008]

EIF4EBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.764

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4EBP1	NM_004095.4 linkuse as main transcript	c.37C>T	p.Arg13Trp	missense_variant	1/3	ENST00000338825.5	NP_004086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4EBP1	ENST00000338825.5 linkuse as main transcript	c.37C>T	p.Arg13Trp	missense_variant	1/3	1	NM_004095.4	ENSP00000340691	P1

Frequencies

GnomAD3 genomes

AF:

0.0000725

AC:

AN:

151650

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000191

AC:

AN:

104818

Hom.:

AF XY:

0.0000343

AC XY:

AN XY:

58328

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000450

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000306

GnomAD4 exome

AF:

0.00000662

AC:

AN:

1358804

Hom.:

Cov.:

AF XY:

0.00000746

AC XY:

AN XY:

669894

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000308

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000187

Gnomad4 OTH exome

AF:

0.0000353

GnomAD4 genome

AF:

0.0000725

AC:

AN:

151650

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74032

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000590

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.000162

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2023

The c.37C>T (p.R13W) alteration is located in exon 1 (coding exon 1) of the EIF4EBP1 gene. This alteration results from a C to T substitution at nucleotide position 37, causing the arginine (R) at amino acid position 13 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.78

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.88

M_CAP

Pathogenic

0.73

MetaRNN

Pathogenic

0.76

MetaSVM

Uncertain

-0.092

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-4.4

REVEL

Uncertain

0.42

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.40

MutPred

0.56

Loss of disorder (P = 0.0142);

MVP

0.50

MPC

0.98

ClinPred

1.0

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.53

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