chr17-80136257-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_014740.4(EIF4A3):c.1062C>T(p.Leu354Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 0 hom. )
Consequence
EIF4A3
NM_014740.4 synonymous
NM_014740.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.230
Genes affected
EIF4A3 (HGNC:18683): (eukaryotic translation initiation factor 4A3) This gene encodes a member of the DEAD box protein family. DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The protein encoded by this gene is a nuclear matrix protein. Its amino acid sequence is highly similar to the amino acid sequences of the translation initiation factors eIF4AI and eIF4AII, two other members of the DEAD box protein family. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 17-80136257-G-A is Benign according to our data. Variant chr17-80136257-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648397.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.23 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EIF4A3 | NM_014740.4 | c.1062C>T | p.Leu354Leu | synonymous_variant | 10/12 | ENST00000649764.2 | NP_055555.1 | |
EIF4A3 | NM_001411099.1 | c.999C>T | p.Leu333Leu | synonymous_variant | 9/11 | NP_001398028.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EIF4A3 | ENST00000649764.2 | c.1062C>T | p.Leu354Leu | synonymous_variant | 10/12 | NM_014740.4 | ENSP00000497641.1 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000286 AC: 72AN: 251414Hom.: 0 AF XY: 0.000294 AC XY: 40AN XY: 135876
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GnomAD4 exome AF: 0.000213 AC: 311AN: 1461808Hom.: 0 Cov.: 31 AF XY: 0.000231 AC XY: 168AN XY: 727220
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GnomAD4 genome AF: 0.000158 AC: 24AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74458
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
EIF4A3-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 21, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | EIF4A3: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at