Variant 5-176645416-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099408.2(EIF4E1B):c.514A>G(p.Arg172Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,370,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

EIF4E1B
NM_001099408.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

Variant links:

Genes affected

EIF4E1B (HGNC:33179): (eukaryotic translation initiation factor 4E family member 1B) Predicted to enable RNA 7-methylguanosine cap binding activity and translation initiation factor activity. Predicted to be involved in regulation of translation and translational initiation. Predicted to be located in cytoplasm. Predicted to be part of eukaryotic translation initiation factor 4F complex and mRNA cap binding activity complex. [provided by Alliance of Genome Resources, Apr 2022]

EIF4E1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07228297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4E1B	NM_001099408.2 linkuse as main transcript	c.514A>G	p.Arg172Gly	missense_variant	8/9	ENST00000318682.11	NP_001092878.1
EIF4E1B	NM_001375362.1 linkuse as main transcript	c.514A>G	p.Arg172Gly	missense_variant	8/9		NP_001362291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4E1B	ENST00000318682.11 linkuse as main transcript	c.514A>G	p.Arg172Gly	missense_variant	8/9	5	NM_001099408.2	ENSP00000323714	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000146

AC:

AN:

1370128

Hom.:

Cov.:

AF XY:

0.00000298

AC XY:

AN XY:

671008

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000188

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000113

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

Oct 04, 2022

The c.514A>G (p.R172G) alteration is located in exon 8 (coding exon 6) of the EIF4E1B gene. This alteration results from a A to G substitution at nucleotide position 514, causing the arginine (R) at amino acid position 172 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.013

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.035

LIST_S2

Uncertain

0.89

.;D;.

M_CAP

Benign

0.0088

MetaRNN

Benign

0.072

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.66

N;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.89

.;N;N

REVEL

Benign

0.18

Sift

Benign

0.045

.;D;D

Sift4G

Uncertain

0.050

.;T;T

Polyphen

0.0

B;B;B

Vest4

0.20

MutPred

0.49

Gain of glycosylation at S171 (P = 0.0469);Gain of glycosylation at S171 (P = 0.0469);Gain of glycosylation at S171 (P = 0.0469);

MVP

0.14

MPC

0.32

ClinPred

0.049

GERP RS

-2.5

Varity_R

0.071

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over