Variant chr10-70404418-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004096.5(EIF4EBP2):c.17G>A(p.Gly6Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00196 in 1,588,236 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 3 hom. )

Consequence

EIF4EBP2
NM_004096.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.94

Variant links:

Genes affected

EIF4EBP2 (HGNC:3289): (eukaryotic translation initiation factor 4E binding protein 2) This gene encodes a member of the eukaryotic translation initiation factor 4E binding protein family. The gene products of this family bind eIF4E and inhibit translation initiation. However, insulin and other growth factors can release this inhibition via a phosphorylation-dependent disruption of their binding to eIF4E. Regulation of protein production through these gene products have been implicated in cell proliferation, cell differentiation and viral infection. [provided by RefSeq, Oct 2008]

EIF4EBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008608103).

BP6

Variant 10-70404418-G-A is Benign according to our data. Variant chr10-70404418-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 777852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 228 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4EBP2	NM_004096.5 linkuse as main transcript	c.17G>A	p.Gly6Asp	missense_variant	1/3	ENST00000373218.5	NP_004087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4EBP2	ENST00000373218.5 linkuse as main transcript	c.17G>A	p.Gly6Asp	missense_variant	1/3	1	NM_004096.5	ENSP00000362314	P1

Frequencies

GnomAD3 genomes

AF:

0.00150

AC:

228

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00222

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00166

AC:

339

AN:

204404

Hom.:

AF XY:

0.00156

AC XY:

177

AN XY:

113774

show subpopulations

Gnomad AFR exome

AF:

0.000214

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00240

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00317

Gnomad NFE exome

AF:

0.00236

Gnomad OTH exome

AF:

0.00202

GnomAD4 exome

AF:

0.00201

AC:

2892

AN:

1435974

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

1397

AN XY:

714002

show subpopulations

Gnomad4 AFR exome

AF:

0.000397

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00233

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00298

Gnomad4 NFE exome

AF:

0.00227

Gnomad4 OTH exome

AF:

0.00184

GnomAD4 genome

AF:

0.00150

AC:

228

AN:

152262

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00222

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00165

Hom.:

Bravo

AF:

0.00144

ESP6500AA

AF:

0.000236

AC:

ESP6500EA

AF:

0.00261

AC:

ExAC

AF:

0.00169

AC:

200

Asia WGS

AF:

0.000290

AC:

AN:

3466

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

-0.095

Eigen_PC

Benign

-0.017

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.57

MetaRNN

Benign

0.0086

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.61

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.73

REVEL

Benign

0.072

Sift

Benign

0.071

Sift4G

Benign

0.44

Polyphen

0.075

Vest4

0.53

MVP

0.47

MPC

0.74

ClinPred

0.027

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.091

gMVP

0.42

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