Genetic Variant NM_004096.5:c.222C>T (chr10-70419990-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_004096.5(EIF4EBP2):c.222C>T(p.His74His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,612,300 control chromosomes in the GnomAD database, including 202,087 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 17933 hom., cov: 31)

Exomes 𝑓: 0.50 ( 184154 hom. )

Consequence

EIF4EBP2
NM_004096.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0500

Publications

25 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP7

Synonymous conserved (PhyloP=-0.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4EBP2	NM_004096.5 link	c.222C>T	p.His74His	synonymous_variant	Exon 2 of 3	ENST00000373218.5	NP_004087.1	Q13542A0A024QZM3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4EBP2	ENST00000373218.5 link	c.222C>T	p.His74His	synonymous_variant	Exon 2 of 3	1	NM_004096.5	ENSP00000362314.4		Q13542

Frequencies

GnomAD3 genomes

AF:

0.480

AC:

72927

AN:

151820

Hom.:

17909

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.482

Gnomad ASJ

AF:

0.391

Gnomad EAS

AF:

0.721

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.495

Gnomad OTH

AF:

0.488

GnomAD2 exomes

AF:

0.497

AC:

124240

AN:

249930

AF XY:

0.499

show subpopulations

Gnomad AFR exome

AF:

0.416

Gnomad AMR exome

AF:

0.422

Gnomad ASJ exome

AF:

0.390

Gnomad EAS exome

AF:

0.729

Gnomad FIN exome

AF:

0.508

Gnomad NFE exome

AF:

0.504

Gnomad OTH exome

AF:

0.492

GnomAD4 exome

AF:

0.500

AC:

730031

AN:

1460364

Hom.:

184154

Cov.:

AF XY:

0.500

AC XY:

363110

AN XY:

726496

show subpopulations

African (AFR)

AF:

0.424

AC:

14157

AN:

33398

American (AMR)

AF:

0.428

AC:

19026

AN:

44486

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

10139

AN:

26094

East Asian (EAS)

AF:

0.686

AC:

27166

AN:

39592

South Asian (SAS)

AF:

0.486

AC:

41732

AN:

85952

European-Finnish (FIN)

AF:

0.510

AC:

27262

AN:

53404

Middle Eastern (MID)

AF:

0.487

AC:

2807

AN:

5766

European-Non Finnish (NFE)

AF:

0.502

AC:

557850

AN:

1111340

Other (OTH)

AF:

0.495

AC:

29892

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

18022

36043

54065

72086

90108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16296

32592

48888

65184

81480

<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:

0.480

AC:

72985

AN:

151936

Hom.:

17933

Cov.:

AF XY:

0.483

AC XY:

35868

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.425

AC:

17597

AN:

41408

American (AMR)

AF:

0.482

AC:

7362

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.391

AC:

1357

AN:

3468

East Asian (EAS)

AF:

0.721

AC:

3734

AN:

5178

South Asian (SAS)

AF:

0.496

AC:

2397

AN:

4832

European-Finnish (FIN)

AF:

0.504

AC:

5304

AN:

10520

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.495

AC:

33602

AN:

67942

Other (OTH)

AF:

0.492

AC:

1037

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1879

3758

5636

7515

9394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.473

Hom.:

7467

Bravo

AF:

0.474

Asia WGS

AF:

0.603

AC:

2096

AN:

3478

EpiCase

AF:

0.491

EpiControl

AF:

0.489

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

6.2

(source)

DANN

Benign

0.64

PhyloP100

-0.050

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over