Genetic Variant EIF4EBP2:p.Ser7Ser (chr10-70404422-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_004096.5(EIF4EBP2):c.21C>T(p.Ser7Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,588,848 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 17 hom. )

Consequence

EIF4EBP2
NM_004096.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.73

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 10-70404422-C-T is Benign according to our data. Variant chr10-70404422-C-T is described in ClinVar as Benign. ClinVar VariationId is 715427.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.73 with no splicing effect.

BS2

High AC in GnomAd4 at 268 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.21C>T	p.Ser7Ser	synonymous	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.21C>T	p.Ser7Ser	synonymous	Exon 1 of 3	ENSP00000362314.4	Q13542
	EIF4EBP2	ENST00000892260.1		c.21C>T	p.Ser7Ser	synonymous	Exon 1 of 2	ENSP00000562319.1

Frequencies

GnomAD3 genomes

AF:

0.00176

AC:

268

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00329

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00257

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00194

AC:

400

AN:

205732

AF XY:

0.00211

show subpopulations

Gnomad AFR exome

AF:

0.000849

Gnomad AMR exome

AF:

0.000497

Gnomad ASJ exome

AF:

0.00126

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00289

Gnomad NFE exome

AF:

0.00270

Gnomad OTH exome

AF:

0.00242

GnomAD4 exome

AF:

0.00250

AC:

3591

AN:

1436552

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

1742

AN XY:

714308

show subpopulations

African (AFR)

AF:

0.000297

AC:

AN:

30278

American (AMR)

AF:

0.000649

AC:

AN:

43174

Ashkenazi Jewish (ASJ)

AF:

0.000945

AC:

AN:

25388

East Asian (EAS)

AF:

0.00

AC:

AN:

37038

South Asian (SAS)

AF:

0.00231

AC:

194

AN:

83970

European-Finnish (FIN)

AF:

0.00294

AC:

149

AN:

50742

Middle Eastern (MID)

AF:

0.00147

AC:

AN:

4074

European-Non Finnish (NFE)

AF:

0.00279

AC:

3074

AN:

1102756

Other (OTH)

AF:

0.00181

AC:

107

AN:

59132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

220

440

659

879

1099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<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:

0.00176

AC:

268

AN:

152296

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

135

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000577

AC:

AN:

41570

American (AMR)

AF:

0.000915

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00329

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00257

AC:

175

AN:

68002

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.00220

Hom.:

Bravo

AF:

0.00153

Asia WGS

AF:

0.00174

AC:

AN:

3464

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

2.7

PromoterAI

-0.037

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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