GeneBe

rs1467449031

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_003907.3(EIF2B5):​c.12T>A​(p.Pro4Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P4P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

EIF2B5
NM_003907.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0350

Publications

0 publications found
Variant links:
Genes affected
EIF2B5 (HGNC:3261): (eukaryotic translation initiation factor 2B subunit epsilon) This gene encodes one of five subunits of eukaryotic translation initiation factor 2B (EIF2B), a GTP exchange factor for eukaryotic initiation factor 2 and an essential regulator for protein synthesis. Mutations in this gene and the genes encoding other EIF2B subunits have been associated with leukoencephalopathy with vanishing white matter. [provided by RefSeq, Nov 2009]
EIF2B5-DT (HGNC:55202): (EIF2B5 divergent transcript)

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP7
Synonymous conserved (PhyloP=-0.035 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003907.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
EIF2B5
NM_003907.3
MANE Select
c.12T>Ap.Pro4Pro
synonymous
Exon 1 of 16NP_003898.2Q13144
EIF2B5-DT
NR_183718.1
n.-136A>T
upstream_gene
N/A
EIF2B5-DT
NR_183719.1
n.-136A>T
upstream_gene
N/A

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
EIF2B5
ENST00000648915.2
MANE Select
c.12T>Ap.Pro4Pro
synonymous
Exon 1 of 16ENSP00000497160.1Q13144
EIF2B5
ENST00000432569.2
TSL:1
c.12T>Ap.Pro4Pro
synonymous
Exon 1 of 2ENSP00000414775.1C9JRD9
EIF2B5
ENST00000481054.5
TSL:1
n.13T>A
non_coding_transcript_exon
Exon 1 of 15

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000524
AC:
1
AN:
190884
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000380
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1427496
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
706428
African (AFR)
AF:
0.00
AC:
0
AN:
33286
American (AMR)
AF:
0.00
AC:
0
AN:
37204
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25392
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38752
South Asian (SAS)
AF:
0.00
AC:
0
AN:
81528
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49954
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5724
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1096380
Other (OTH)
AF:
0.00
AC:
0
AN:
59276
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
CADD
Benign
13
DANN
Benign
0.77
PhyloP100
-0.035
PromoterAI
-0.0035
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1467449031; hg19: chr3-183853185; API