4-98881149-GAAA-GA
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_001968.5(EIF4E):c.540-9_540-8delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,139,292 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000048 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
EIF4E
NM_001968.5 splice_region, intron
NM_001968.5 splice_region, intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.94
Publications
0 publications found
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 Gene-Disease associations (from GenCC):
- autism, susceptibility to, 19Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001968.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| EIF4E | NM_001968.5 | MANE Select | c.540-9_540-8delTT | splice_region intron | N/A | NP_001959.1 | P06730-1 | ||
| EIF4E | NM_001130679.3 | c.633-9_633-8delTT | splice_region intron | N/A | NP_001124151.1 | P06730-2 | |||
| EIF4E | NM_001331017.2 | c.624-9_624-8delTT | splice_region intron | N/A | NP_001317946.1 | D6RBW1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| EIF4E | ENST00000450253.7 | TSL:1 MANE Select | c.540-9_540-8delTT | splice_region intron | N/A | ENSP00000389624.2 | P06730-1 | ||
| EIF4E | ENST00000280892.10 | TSL:1 | c.600-9_600-8delTT | splice_region intron | N/A | ENSP00000280892.6 | P06730-3 | ||
| EIF4E | ENST00000505992.1 | TSL:5 | c.633-9_633-8delTT | splice_region intron | N/A | ENSP00000425561.1 | P06730-2 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 122118Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
0
AN:
122118
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.000258 AC: 24AN: 92850 AF XY: 0.000243 show subpopulations
GnomAD2 exomes
AF:
AC:
24
AN:
92850
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.0000483 AC: 55AN: 1139292Hom.: 0 AF XY: 0.0000478 AC XY: 27AN XY: 565364 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
55
AN:
1139292
Hom.:
AF XY:
AC XY:
27
AN XY:
565364
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
3
AN:
26590
American (AMR)
AF:
AC:
4
AN:
31696
Ashkenazi Jewish (ASJ)
AF:
AC:
2
AN:
19112
East Asian (EAS)
AF:
AC:
2
AN:
28188
South Asian (SAS)
AF:
AC:
5
AN:
63552
European-Finnish (FIN)
AF:
AC:
3
AN:
39588
Middle Eastern (MID)
AF:
AC:
0
AN:
4678
European-Non Finnish (NFE)
AF:
AC:
30
AN:
879718
Other (OTH)
AF:
AC:
6
AN:
46170
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.236
Heterozygous variant carriers
0
9
19
28
38
47
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
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>80
Age
GnomAD4 genome 0.00 AC: 0AN: 122140Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 58676
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
122140
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
58676
African (AFR)
AF:
AC:
0
AN:
32610
American (AMR)
AF:
AC:
0
AN:
12314
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2970
East Asian (EAS)
AF:
AC:
0
AN:
4310
South Asian (SAS)
AF:
AC:
0
AN:
3984
European-Finnish (FIN)
AF:
AC:
0
AN:
6720
Middle Eastern (MID)
AF:
AC:
0
AN:
232
European-Non Finnish (NFE)
AF:
AC:
0
AN:
56538
Other (OTH)
AF:
AC:
0
AN:
1730
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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