NM_198241.3:c.481A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_198241.3(EIF4G1):c.481A>G(p.Thr161Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,608,254 control chromosomes in the GnomAD database, including 799,127 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 1.0 ( 75806 hom., cov: 31)

Exomes 𝑓: 1.0 ( 723321 hom. )

Consequence

EIF4G1
NM_198241.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:4

Conservation

PhyloP100: 0.747

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.539281E-7).

BP6

Variant 3-184319745-A-G is Benign according to our data. Variant chr3-184319745-A-G is described in ClinVar as [Benign]. Clinvar id is 1174883.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-184319745-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4G1	NM_198241.3 link	c.481A>G	p.Thr161Ala	missense_variant	Exon 7 of 33	ENST00000346169.7	NP_937884.2	Q04637-1Q96I65

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4G1	ENST00000346169.7 link	c.481A>G	p.Thr161Ala	missense_variant	Exon 7 of 33	1	NM_198241.3	ENSP00000316879.5		Q04637-1

Frequencies

GnomAD3 genomes

AF:

0.998

AC:

151798

AN:

152104

Hom.:

75747

Cov.:

show subpopulations

Gnomad AFR

AF:

0.999

Gnomad AMI

AF:

0.997

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

0.997

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.997

Gnomad OTH

AF:

0.999

GnomAD3 exomes

AF:

0.998

AC:

239825

AN:

240302

Hom.:

119676

AF XY:

0.998

AC XY:

129774

AN XY:

130056

show subpopulations

Gnomad AFR exome

AF:

0.999

Gnomad AMR exome

AF:

0.999

Gnomad ASJ exome

AF:

0.999

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.997

Gnomad NFE exome

AF:

0.997

Gnomad OTH exome

AF:

0.998

GnomAD4 exome

AF:

0.997

AC:

1451328

AN:

1456032

Hom.:

723321

Cov.:

AF XY:

0.997

AC XY:

721286

AN XY:

723592

show subpopulations

Gnomad4 AFR exome

AF:

0.999

Gnomad4 AMR exome

AF:

0.999

Gnomad4 ASJ exome

AF:

0.999

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

0.997

Gnomad4 NFE exome

AF:

0.996

Gnomad4 OTH exome

AF:

0.998

GnomAD4 genome

AF:

0.998

AC:

151916

AN:

152222

Hom.:

75806

Cov.:

AF XY:

0.998

AC XY:

74268

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.999

Gnomad4 AMR

AF:

1.00

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

0.997

Gnomad4 NFE

AF:

0.997

Gnomad4 OTH

AF:

0.999

Alfa

AF:

0.998

Hom.:

90307

Bravo

AF:

0.998

TwinsUK

AF:

0.997

AC:

3698

ALSPAC

AF:

0.998

AC:

3846

ESP6500AA

AF:

0.999

AC:

4402

ESP6500EA

AF:

0.996

AC:

8567

ExAC

AF:

0.997

AC:

120710

Asia WGS

AF:

1.00

AC:

3477

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.9

DANN

Benign

0.81

DEOGEN2

Benign

0.063

T;.;.;.;.;T;.;T;.;T;.;.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.092

T;T;T;T;T;T;.;T;T;T;T;.;T;T

MetaRNN

Benign

5.5e-7

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.2

N;.;.;.;.;.;.;.;.;.;N;.;.;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.69

N;N;N;N;N;N;N;N;.;N;N;N;N;N

REVEL

Benign

0.036

Sift

Benign

1.0

T;T;T;T;T;T;T;T;.;T;T;T;T;T

Sift4G

Benign

0.93

T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.034

MPC

0.63

ClinPred

0.0019

GERP RS

-1.8

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.8

Varity_R

0.050

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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