rs1406170008
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_198241.3(EIF4G1):c.32delC(p.Pro11HisfsTer31) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,392,498 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )
Consequence
EIF4G1
NM_198241.3 frameshift
NM_198241.3 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.33
Publications
0 publications found
Genes affected
EIF4G1 (HGNC:3296): (eukaryotic translation initiation factor 4 gamma 1) The protein encoded by this gene is a component of the multi-subunit protein complex EIF4F. This complex facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. The recognition of the mRNA cap and the ATP-dependent unwinding of 5'-terminal secondary structure is catalyzed by factors in this complex. The subunit encoded by this gene is a large scaffolding protein that contains binding sites for other members of the EIF4F complex. A domain at its N-terminus can also interact with the poly(A)-binding protein, which may mediate the circularization of mRNA during translation. Alternative splicing results in multiple transcript variants, some of which are derived from alternative promoter usage. [provided by RefSeq, Aug 2010]
EIF4G1 Gene-Disease associations (from GenCC):
- Parkinson disease 18, autosomal dominant, susceptibility toInheritance: Unknown, AD Classification: MODERATE, LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.993 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_198241.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| EIF4G1 | MANE Select | c.32delC | p.Pro11HisfsTer31 | frameshift | Exon 3 of 33 | NP_937884.2 | Q04637-1 | ||
| EIF4G1 | c.32delC | p.Pro11HisfsTer31 | frameshift | Exon 3 of 34 | NP_001181875.2 | Q04637-9 | |||
| EIF4G1 | c.32delC | p.Pro11HisfsTer31 | frameshift | Exon 2 of 33 | NP_001181876.2 | Q04637-9 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| EIF4G1 | TSL:1 MANE Select | c.32delC | p.Pro11HisfsTer31 | frameshift | Exon 3 of 33 | ENSP00000316879.5 | Q04637-1 | ||
| EIF4G1 | TSL:1 | c.32delC | p.Pro11HisfsTer31 | frameshift | Exon 2 of 33 | ENSP00000338020.4 | Q04637-9 | ||
| EIF4G1 | TSL:1 | c.32delC | p.Pro11HisfsTer31 | frameshift | Exon 3 of 34 | ENSP00000371767.3 | Q04637-9 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.18e-7 AC: 1AN: 1392498Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 687170 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1392498
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
687170
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
31496
American (AMR)
AF:
AC:
0
AN:
35732
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25132
East Asian (EAS)
AF:
AC:
0
AN:
35746
South Asian (SAS)
AF:
AC:
0
AN:
79130
European-Finnish (FIN)
AF:
AC:
0
AN:
49018
Middle Eastern (MID)
AF:
AC:
0
AN:
5644
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1072858
Other (OTH)
AF:
AC:
0
AN:
57742
⚠️ 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: 0.175
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
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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