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chr4-98928975-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000280892.10(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 (★).

Frequency

Genomes: 𝑓 0.56 ( 26336 hom., cov: 32)
Exomes 𝑓: 0.44 ( 145061 hom. )

Consequence

EIF4E
ENST00000280892.10 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter 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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EIF4ENM_001968.5 linkuse as main transcriptc.18+120T>C intron_variant ENST00000450253.7
EIF4ENM_001130678.4 linkuse as main transcriptc.-3T>C 5_prime_UTR_variant 1/7
EIF4ENM_001130679.3 linkuse as main transcriptc.18+120T>C intron_variant
EIF4ENM_001331017.2 linkuse as main transcriptc.-181+120T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EIF4EENST00000450253.7 linkuse as main transcriptc.18+120T>C intron_variant 1 NM_001968.5 P1P06730-1
ENST00000583654.1 linkuse as main transcriptn.62+17A>G intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.560
AC:
85023
AN:
151856
Hom.:
26276
Cov.:
32
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.:
60
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.:
32
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

EIF4E-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This 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
17
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.

Other links and lift over

dbSNP: rs11723037; hg19: chr4-99850126; COSMIC: COSV55186293; API