Genetic Variant NM_003907.3:c.26C>G (chr3-184135411-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003907.3(EIF2B5):c.26C>G(p.Pro9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000042 in 1,429,514 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 (★). Synonymous variant affecting the same amino acid position (i.e. P9P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

EIF2B5
NM_003907.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34

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 links:

EIF2B5-DT (HGNC:55202): (EIF2B5 divergent transcript)

EIF2B5-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1984795).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF2B5	NM_003907.3	MANE Select	c.26C>G	p.Pro9Arg	missense	Exon 1 of 16	NP_003898.2	Q13144
EIF2B5-DT	NR_183718.1		n.-150G>C		upstream_gene	N/A
EIF2B5-DT	NR_183719.1		n.-150G>C		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF2B5	ENST00000648915.2	MANE Select	c.26C>G	p.Pro9Arg	missense	Exon 1 of 16	ENSP00000497160.1	Q13144
EIF2B5	ENST00000432569.2	TSL:1	c.26C>G	p.Pro9Arg	missense	Exon 1 of 2	ENSP00000414775.1	C9JRD9
EIF2B5	ENST00000481054.5	TSL:1	n.27C>G		non_coding_transcript_exon	Exon 1 of 15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000420

AC:

AN:

1429514

Hom.:

Cov.:

AF XY:

0.00000424

AC XY:

AN XY:

707716

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33302

American (AMR)

AF:

0.00

AC:

AN:

37568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25410

East Asian (EAS)

AF:

0.00

AC:

AN:

38764

South Asian (SAS)

AF:

0.00

AC:

AN:

81706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00000456

AC:

AN:

1097528

Other (OTH)

AF:

0.0000169

AC:

AN:

59326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.049

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.59

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.20

MetaSVM

Uncertain

0.26

MutationAssessor

Benign

0.20

PhyloP100

1.3

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.27

REVEL

Uncertain

0.35

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.43

Vest4

0.36

MVP

0.49

MPC

0.30

ClinPred

0.48

GERP RS

4.1

PromoterAI

-0.084

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.51

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over