Genetic Variant NM_004096.5:c.17G>A (chr10-70404418-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 777852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 228 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004096.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4EBP2	NM_004096.5	MANE Select	c.17G>A	p.Gly6Asp	missense	Exon 1 of 3	NP_004087.1	Q13542

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4EBP2	ENST00000373218.5	TSL:1 MANE Select	c.17G>A	p.Gly6Asp	missense	Exon 1 of 3	ENSP00000362314.4	Q13542
	EIF4EBP2	ENST00000892260.1		c.17G>A	p.Gly6Asp	missense	Exon 1 of 2	ENSP00000562319.1

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

GnomAD2 exomes

AF:

0.00166

AC:

339

AN:

204404

AF XY:

0.00156

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 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

African (AFR)

AF:

0.000397

AC:

AN:

30252

American (AMR)

AF:

0.00130

AC:

AN:

43126

Ashkenazi Jewish (ASJ)

AF:

0.00233

AC:

AN:

25376

East Asian (EAS)

AF:

0.00

AC:

AN:

36998

South Asian (SAS)

AF:

0.00

AC:

AN:

83936

European-Finnish (FIN)

AF:

0.00298

AC:

151

AN:

50728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4078

European-Non Finnish (NFE)

AF:

0.00227

AC:

2505

AN:

1102360

Other (OTH)

AF:

0.00184

AC:

109

AN:

59120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

189

378

567

756

945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00150

AC:

228

AN:

152262

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41552

American (AMR)

AF:

0.00137

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00222

AC:

151

AN:

67996

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

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

PhyloP100

3.9

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

PromoterAI

-0.0055

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.091

gMVP

0.42

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over