rs2293605
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000346169.7(EIF4G1):c.3325+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,606,692 control chromosomes in the GnomAD database, including 10,986 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.090 ( 810 hom., cov: 33)
Exomes 𝑓: 0.12 ( 10176 hom. )
Consequence
EIF4G1
ENST00000346169.7 intron
ENST00000346169.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.672
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 3-184326645-C-T is Benign according to our data. Variant chr3-184326645-C-T is described in ClinVar as [Benign]. Clinvar id is 518345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-184326645-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EIF4G1 | NM_198241.3 | c.3325+16C>T | intron_variant | ENST00000346169.7 | NP_937884.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EIF4G1 | ENST00000346169.7 | c.3325+16C>T | intron_variant | 1 | NM_198241.3 | ENSP00000316879 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0897 AC: 13653AN: 152170Hom.: 811 Cov.: 33
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GnomAD3 exomes AF: 0.106 AC: 26125AN: 245644Hom.: 1624 AF XY: 0.109 AC XY: 14492AN XY: 133300
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GnomAD4 exome AF: 0.115 AC: 167486AN: 1454404Hom.: 10176 Cov.: 32 AF XY: 0.116 AC XY: 83893AN XY: 723818
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GnomAD4 genome AF: 0.0896 AC: 13648AN: 152288Hom.: 810 Cov.: 33 AF XY: 0.0908 AC XY: 6761AN XY: 74460
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2021 | - - |
Parkinson disease 18, autosomal dominant, susceptibility to Benign:1
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at