Variant 4-98928975-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001130678.4(EIF4E):c.-3T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,573,108 control chromosomes in the GnomAD database, including 171,397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.56 ( 26336 hom., cov: 32)

Exomes 𝑓: 0.44 ( 145061 hom. )

Consequence

EIF4E
NM_001130678.4 5_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.04

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:

EIF4E (HGNC:):

EIF4E links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 4-98928975-A-G is Benign according to our data. Variant chr4-98928975-A-G is described in ClinVar as [Benign]. Clinvar id is 3061014.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
EIF4E	NM_001968.5 linkuse as main transcript	c.18+120T>C	intron_variant		ENST00000450253.7	NP_001959.1	P06730-1
EIF4E	NM_001130678.4 linkuse as main transcript	c.-3T>C	5_prime_UTR_variant	1/7		NP_001124150.1	P06730-3Q32Q75X5D7E3
EIF4E	NM_001130679.3 linkuse as main transcript	c.18+120T>C	intron_variant			NP_001124151.1	P06730-2
EIF4E	NM_001331017.2 linkuse as main transcript	c.-181+120T>C	intron_variant			NP_001317946.1	P06730D6RBW1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4E	ENST00000450253.7 linkuse as main transcript	c.18+120T>C		intron_variant		1	NM_001968.5	ENSP00000389624.2		P06730-1

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

85023

AN:

151856

Hom.:

26276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.836

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.503

Gnomad ASJ

AF:

0.501

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.430

Gnomad OTH

AF:

0.555

GnomAD3 exomes

AF:

0.467

AC:

86136

AN:

184418

Hom.:

21377

AF XY:

0.457

AC XY:

45649

AN XY:

99890

show subpopulations

Gnomad AFR exome

AF:

0.837

Gnomad AMR exome

AF:

0.476

Gnomad ASJ exome

AF:

0.495

Gnomad EAS exome

AF:

0.672

Gnomad SAS exome

AF:

0.387

Gnomad FIN exome

AF:

0.435

Gnomad NFE exome

AF:

0.416

Gnomad OTH exome

AF:

0.454

GnomAD4 exome

AF:

0.444

AC:

630993

AN:

1421134

Hom.:

145061

Cov.:

AF XY:

0.441

AC XY:

310194

AN XY:

703134

show subpopulations

Gnomad4 AFR exome

AF:

0.851

Gnomad4 AMR exome

AF:

0.485

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.689

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.439

Gnomad4 NFE exome

AF:

0.423

Gnomad4 OTH exome

AF:

0.475

GnomAD4 genome

AF:

0.560

AC:

85151

AN:

151974

Hom.:

26336

Cov.:

AF XY:

0.556

AC XY:

41325

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.836

Gnomad4 AMR

AF:

0.503

Gnomad4 ASJ

AF:

0.501

Gnomad4 EAS

AF:

0.684

Gnomad4 SAS

AF:

0.398

Gnomad4 FIN

AF:

0.451

Gnomad4 NFE

AF:

0.430

Gnomad4 OTH

AF:

0.555

Alfa

AF:

0.464

Hom.:

34503

Bravo

AF:

0.581

Asia WGS

AF:

0.524

AC:

1826

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EIF4E-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.67

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over