Variant 1-20807343-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001391906.1(EIF4G3):c.4902A>G(p.Ala1634Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00729 in 1,605,852 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 52 hom. )

Consequence

EIF4G3
NM_001391906.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.74

Variant links:

Genes affected

EIF4G3 (HGNC:3298): (eukaryotic translation initiation factor 4 gamma 3) The protein encoded by this gene is thought to be part of the eIF4F protein complex, which is involved in mRNA cap recognition and transport of mRNAs to the ribosome. Interestingly, a microRNA (miR-520c-3p) has been found that negatively regulates synthesis of the encoded protein, and this leads to a global decrease in protein translation and cell proliferation. Therefore, this protein is a key component of the anti-tumor activity of miR-520c-3p. [provided by RefSeq, May 2016]

EIF4G3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 1-20807343-T-C is Benign according to our data. Variant chr1-20807343-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2638442.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.74 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4G3	NM_001391906.1 link	c.4902A>G	p.Ala1634Ala	synonymous_variant	Exon 37 of 37	ENST00000602326.6	NP_001378835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4G3	ENST00000602326.6 link	c.4902A>G	p.Ala1634Ala	synonymous_variant	Exon 37 of 37	1	NM_001391906.1	ENSP00000473510.2		A0A8J9G7U8

Frequencies

GnomAD3 genomes

AF:

0.00572

AC:

871

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00703

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00825

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00604

AC:

1505

AN:

249166

Hom.:

AF XY:

0.00653

AC XY:

879

AN XY:

134708

show subpopulations

Gnomad AFR exome

AF:

0.00321

Gnomad AMR exome

AF:

0.00367

Gnomad ASJ exome

AF:

0.00339

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00783

Gnomad FIN exome

AF:

0.00610

Gnomad NFE exome

AF:

0.00763

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.00746

AC:

10837

AN:

1453516

Hom.:

Cov.:

AF XY:

0.00757

AC XY:

5463

AN XY:

722048

show subpopulations

Gnomad4 AFR exome

AF:

0.00261

Gnomad4 AMR exome

AF:

0.00409

Gnomad4 ASJ exome

AF:

0.00296

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00782

Gnomad4 FIN exome

AF:

0.00603

Gnomad4 NFE exome

AF:

0.00812

Gnomad4 OTH exome

AF:

0.00771

GnomAD4 genome

AF:

0.00571

AC:

870

AN:

152336

Hom.:

Cov.:

AF XY:

0.00564

AC XY:

420

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00274

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00683

Gnomad4 FIN

AF:

0.00537

Gnomad4 NFE

AF:

0.00825

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00696

Hom.:

Bravo

AF:

0.00533

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EIF4G3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.5

DANN

Benign

0.53

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