Variant rs2293605 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198241.3(EIF4G1):c.3325+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,606,692 control chromosomes in the GnomAD database, including 10,986 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.090 ( 810 hom., cov: 33)

Exomes 𝑓: 0.12 ( 10176 hom. )

Consequence

EIF4G1
NM_198241.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.672

Variant links:

Genes affected

EIF4G1 (HGNC:3296): (eukaryotic translation initiation factor 4 gamma 1) The protein encoded by this gene is a component of the multi-subunit protein complex EIF4F. This complex facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. The recognition of the mRNA cap and the ATP-dependent unwinding of 5'-terminal secondary structure is catalyzed by factors in this complex. The subunit encoded by this gene is a large scaffolding protein that contains binding sites for other members of the EIF4F complex. A domain at its N-terminus can also interact with the poly(A)-binding protein, which may mediate the circularization of mRNA during translation. Alternative splicing results in multiple transcript variants, some of which are derived from alternative promoter usage. [provided by RefSeq, Aug 2010]

EIF4G1 links:

EIF4G1 (HGNC:):

EIF4G1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-184326645-C-T is Benign according to our data. Variant chr3-184326645-C-T is described in ClinVar as [Benign]. Clinvar id is 518345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-184326645-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4G1	NM_198241.3 linkuse as main transcript	c.3325+16C>T		intron_variant		ENST00000346169.7	NP_937884.2	Q04637-1Q96I65

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4G1	ENST00000346169.7 linkuse as main transcript	c.3325+16C>T		intron_variant		1	NM_198241.3	ENSP00000316879.5		Q04637-1

Frequencies

GnomAD3 genomes

AF:

0.0897

AC:

13653

AN:

152170

Hom.:

811

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0895

Gnomad ASJ

AF:

0.0983

Gnomad EAS

AF:

0.0262

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.0876

GnomAD3 exomes

AF:

0.106

AC:

26125

AN:

245644

Hom.:

1624

AF XY:

0.109

AC XY:

14492

AN XY:

133300

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.0293

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.115

AC:

167486

AN:

1454404

Hom.:

10176

Cov.:

AF XY:

0.116

AC XY:

83893

AN XY:

723818

show subpopulations

Gnomad4 AFR exome

AF:

0.0178

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.0179

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.165

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.0896

AC:

13648

AN:

152288

Hom.:

810

Cov.:

AF XY:

0.0908

AC XY:

6761

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0214

Gnomad4 AMR

AF:

0.0893

Gnomad4 ASJ

AF:

0.0983

Gnomad4 EAS

AF:

0.0266

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.165

Gnomad4 NFE

AF:

0.124

Gnomad4 OTH

AF:

0.0863

Alfa

AF:

0.111

Hom.:

580

Bravo

AF:

0.0801

Asia WGS

AF:

0.0470

AC:

163

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Parkinson disease 18, autosomal dominant, susceptibility to

Benign:1

Benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.13

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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