chr12-53040160-C-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001417.7(EIF4B):c.1773C>G(p.Ser591Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000139 in 1,614,160 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
EIF4B
NM_001417.7 missense
NM_001417.7 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 3.95
Genes affected
EIF4B (HGNC:3285): (eukaryotic translation initiation factor 4B) Enables RNA binding activity. Predicted to be involved in eukaryotic translation initiation factor 4F complex assembly and formation of translation preinitiation complex. Located in cytosol. Biomarker of autism spectrum disorder and major depressive disorder. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, EIF4B
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2607757).
BS2
?
High AC in GnomAd at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EIF4B | NM_001417.7 | c.1773C>G | p.Ser591Arg | missense_variant | 15/15 | ENST00000262056.14 | |
EIF4B | NM_001300821.3 | c.1788C>G | p.Ser596Arg | missense_variant | 15/15 | ||
EIF4B | NM_001330654.2 | c.1656C>G | p.Ser552Arg | missense_variant | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EIF4B | ENST00000262056.14 | c.1773C>G | p.Ser591Arg | missense_variant | 15/15 | 1 | NM_001417.7 | P4 | |
TNS2-AS1 | ENST00000552905.6 | n.320+5801G>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152196Hom.: 0 Cov.: 33
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?
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GnomAD3 exomes AF: 0.000132 AC: 33AN: 249508Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135376
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GnomAD4 exome AF: 0.000143 AC: 209AN: 1461846Hom.: 0 Cov.: 31 AF XY: 0.000151 AC XY: 110AN XY: 727224
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74484
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The c.1773C>G (p.S591R) alteration is located in exon 15 (coding exon 15) of the EIF4B gene. This alteration results from a C to G substitution at nucleotide position 1773, causing the serine (S) at amino acid position 591 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;B;.
Vest4
MutPred
0.28
.;Loss of ubiquitination at K591 (P = 0.0157);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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