Variant chr4-98886531-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001968.5(EIF4E):c.399+548A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 426,924 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 1 hom. )

Consequence

EIF4E
NM_001968.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004441768).

BP6

Variant 4-98886531-T-C is Benign according to our data. Variant chr4-98886531-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 720923.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 403 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EIF4E	NM_001968.5 linkuse as main transcript	c.399+548A>G		intron_variant		ENST00000450253.7
EIF4E	NM_001130679.3 linkuse as main transcript	c.415A>G	p.Met139Val	missense_variant	6/8
EIF4E	NM_001130678.4 linkuse as main transcript	c.459+548A>G		intron_variant
EIF4E	NM_001331017.2 linkuse as main transcript	c.483+548A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4E	ENST00000450253.7 linkuse as main transcript	c.399+548A>G		intron_variant		1	NM_001968.5	P1	P06730-1

Frequencies

GnomAD3 genomes

AF:

0.00264

AC:

401

AN:

151656

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00790

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00528

GnomAD3 exomes

AF:

0.000684

AC:

AN:

112498

Hom.:

AF XY:

0.000522

AC XY:

AN XY:

61310

show subpopulations

Gnomad AFR exome

AF:

0.00774

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000162

Gnomad OTH exome

AF:

0.000870

GnomAD4 exome

AF:

0.000498

AC:

137

AN:

275150

Hom.:

Cov.:

AF XY:

0.000372

AC XY:

AN XY:

155812

show subpopulations

Gnomad4 AFR exome

AF:

0.00827

Gnomad4 AMR exome

AF:

0.00122

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000551

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000199

Gnomad4 OTH exome

AF:

0.000942

GnomAD4 genome

AF:

0.00266

AC:

403

AN:

151774

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

188

AN XY:

74166

show subpopulations

Gnomad4 AFR

AF:

0.00793

Gnomad4 AMR

AF:

0.00223

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.0000857

Hom.:

Bravo

AF:

0.00320

ExAC

AF:

0.000324

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.8

DANN

Benign

0.33

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0044

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Benign

-0.020

REVEL

Benign

0.025

Sift

Uncertain

0.029

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.12

MutPred

0.56

Loss of solvent accessibility (P = 0.0249);

MVP

0.33

MPC

1.1

ClinPred

0.022

GERP RS

-1.8

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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