Genetic Variant EIF4G1:c.425-224_425-223delGT (chr3-184319426-GGT-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_198241.3(EIF4G1):c.425-224_425-223delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.029 ( 36 hom., cov: 0)

Consequence

EIF4G1
NM_198241.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.764

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 3-184319426-GGT-G is Benign according to our data. Variant chr3-184319426-GGT-G is described in ClinVar as Benign. ClinVar VariationId is 1183465.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0292 (3301/112874) while in subpopulation EAS AF = 0.0513 (210/4096). AF 95% confidence interval is 0.0456. There are 36 homozygotes in GnomAd4. There are 1632 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 3301 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198241.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EIF4G1	NM_198241.3	MANE Select	c.425-224_425-223delGT	intron	N/A	NP_937884.2	Q04637-1
EIF4G1	NM_001194946.2		c.446-224_446-223delGT	intron	N/A	NP_001181875.2	Q04637-9
EIF4G1	NM_001194947.2		c.446-224_446-223delGT	intron	N/A	NP_001181876.2	Q04637-9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EIF4G1	ENST00000346169.7	TSL:1 MANE Select	c.425-262_425-261delGT	intron	N/A	ENSP00000316879.5	Q04637-1
EIF4G1	ENST00000352767.7	TSL:1	c.446-262_446-261delGT	intron	N/A	ENSP00000338020.4	Q04637-9
EIF4G1	ENST00000382330.7	TSL:1	c.446-262_446-261delGT	intron	N/A	ENSP00000371767.3	Q04637-9

Frequencies

GnomAD3 genomes

AF:

0.0292

AC:

3297

AN:

112786

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00796

Gnomad AMI

AF:

0.00938

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.00941

Gnomad EAS

AF:

0.0511

Gnomad SAS

AF:

0.0297

Gnomad FIN

AF:

0.0500

Gnomad MID

AF:

0.00800

Gnomad NFE

AF:

0.0385

Gnomad OTH

AF:

0.0258

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0292

AC:

3301

AN:

112874

Hom.:

Cov.:

AF XY:

0.0302

AC XY:

1632

AN XY:

54116

show subpopulations

African (AFR)

AF:

0.00793

AC:

215

AN:

27120

American (AMR)

AF:

0.0200

AC:

220

AN:

11010

Ashkenazi Jewish (ASJ)

AF:

0.00941

AC:

AN:

2658

East Asian (EAS)

AF:

0.0513

AC:

210

AN:

4096

South Asian (SAS)

AF:

0.0298

AC:

103

AN:

3452

European-Finnish (FIN)

AF:

0.0500

AC:

367

AN:

7336

Middle Eastern (MID)

AF:

0.00855

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.0385

AC:

2111

AN:

54812

Other (OTH)

AF:

0.0291

AC:

AN:

1410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

133

266

399

532

665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0106

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.76

Mutation Taster

=100/0

polymorphism

(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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3-184319426-GGTGTGTGTGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGTGTGTGTGT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over