Variant rs201302296 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130679.3(EIF4E):c.415A>T(p.Met139Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000468 in 426,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

EIF4E
NM_001130679.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.792

Variant links:

Genes affected

EIF4E (HGNC:3287): (eukaryotic translation initiation factor 4E) The protein encoded by this gene is a component of the eukaryotic translation initiation factor 4F complex, which recognizes the 7-methylguanosine cap structure at the 5' end of messenger RNAs. The encoded protein aids in translation initiation by recruiting ribosomes to the 5'-cap structure. Association of this protein with the 4F complex is the rate-limiting step in translation initiation. This gene acts as a proto-oncogene, and its expression and activation is associated with transformation and tumorigenesis. Several pseudogenes of this gene are found on other chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

EIF4E links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.073277354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4E	NM_001968.5 link	c.399+548A>T		intron_variant	Intron 5 of 6	ENST00000450253.7	NP_001959.1	P06730-1
EIF4E	NM_001130679.3 link	c.415A>T	p.Met139Leu	missense_variant	Exon 6 of 8		NP_001124151.1	P06730-2
EIF4E	NM_001331017.2 link	c.483+548A>T		intron_variant	Intron 6 of 7		NP_001317946.1	P06730D6RBW1
EIF4E	NM_001130678.4 link	c.459+548A>T		intron_variant	Intron 5 of 6		NP_001124150.1	P06730-3Q32Q75X5D7E3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4E	ENST00000450253.7 link	c.399+548A>T		intron_variant	Intron 5 of 6	1	NM_001968.5	ENSP00000389624.2		P06730-1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151656

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.00000363

AC:

AN:

275152

Hom.:

Cov.:

AF XY:

0.00000642

AC XY:

AN XY:

155812

show subpopulations

Gnomad4 AFR exome

AF:

0.000133

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151774

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74166

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

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:

0.00

ExAC

AF:

0.0000648

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.48

DANN

Benign

0.23

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.50

M_CAP

Benign

0.0035

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.020

REVEL

Benign

0.023

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.19

MutPred

0.58

Loss of solvent accessibility (P = 0.0249);

MVP

0.39

MPC

1.1

ClinPred

0.069

GERP RS

-1.8

gMVP

0.71

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over