rs2293605

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

Parkinson disease 18, autosomal dominant, susceptibility to
Inheritance: Unknown, AD Classification: MODERATE, LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

EIF4G1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 518345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
EIF4G1	NM_198241.3 link	c.3325+16C>T		intron_variant	Intron 22 of 32	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.3325+16C>T		intron_variant	Intron 22 of 32	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

GnomAD2 exomes

AF:

0.106

AC:

26125

AN:

245644

AF XY:

0.109

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 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

African (AFR)

AF:

0.0178

AC:

595

AN:

33476

American (AMR)

AF:

0.108

AC:

4832

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

2743

AN:

26130

East Asian (EAS)

AF:

0.0179

AC:

710

AN:

39696

South Asian (SAS)

AF:

0.105

AC:

9070

AN:

86176

European-Finnish (FIN)

AF:

0.165

AC:

7662

AN:

46408

Middle Eastern (MID)

AF:

0.0807

AC:

462

AN:

5722

European-Non Finnish (NFE)

AF:

0.122

AC:

135293

AN:

1111754

Other (OTH)

AF:

0.101

AC:

6119

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

8255

16510

24764

33019

41274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4766

9532

14298

19064

23830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0896

AC:

13648

AN:

152288

Hom.:

810

Cov.:

AF XY:

0.0908

AC XY:

6761

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0214

AC:

891

AN:

41578

American (AMR)

AF:

0.0893

AC:

1366

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0983

AC:

341

AN:

3470

East Asian (EAS)

AF:

0.0266

AC:

138

AN:

5186

South Asian (SAS)

AF:

0.106

AC:

511

AN:

4828

European-Finnish (FIN)

AF:

0.165

AC:

1745

AN:

10588

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.124

AC:

8453

AN:

68026

Other (OTH)

AF:

0.0863

AC:

182

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

648

1296

1945

2593

3241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.100

Hom.:

789

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

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Parkinson disease 18, autosomal dominant, susceptibility to

Benign:1

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.13

(source)

DANN

Benign

0.52

PhyloP100

-0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over