chr1-20817449-G-A

Variant names:

• chr1-20817449-G-A
• rs138556551
• NM_001391906.1:c.4458C>T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001391906.1(EIF4G3):​c.4458C>T​(p.Leu1486Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000712 in 1,609,172 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00071 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (3 hom.)
• Consequence: EIF4G3 NM_001391906.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.14

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-20817449-G-A is Benign according to our data. Variant chr1-20817449-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3250528.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.14 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4G3	NM_001391906.1	c.4458C>T	p.Leu1486Leu	synonymous_variant	Exon 34 of 37	ENST00000602326.6	NP_001378835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4G3	ENST00000602326.6	c.4458C>T	p.Leu1486Leu	synonymous_variant	Exon 34 of 37	1	NM_001391906.1	ENSP00000473510.2

Frequencies

GnomAD3 genomes AF: 0.000707 AC: 107 AN: 151410 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000723

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000590

Gnomad OTH AF: 0.00242

GnomAD3 exomes AF: 0.000845 AC: 212 AN: 250884 Hom.: 3 AF XY: 0.000782 AC XY: 106 AN XY: 135600

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000926

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000476

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000712 AC: 1038 AN: 1457646 Hom.: 3 Cov.: 30 AF XY: 0.000714 AC XY: 518 AN XY: 725116

Gnomad4 AFR exome AF: 0.0000898

Gnomad4 AMR exome AF: 0.000940

Gnomad4 ASJ exome AF: 0.0101

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000556

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.000706 AC: 107 AN: 151526 Hom.: 1 Cov.: 32 AF XY: 0.000824 AC XY: 61 AN XY: 74048

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000722

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000590

Gnomad4 OTH AF: 0.00239

Alfa AF: 0.00121 Hom.: 1

Bravo AF: 0.000801

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EIF4G3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.047
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs138556551; hg19: chr1-21143942; COSMIC: COSV51680059;