Genetic Variant EIF3G:c.596-260T>C (chr19-10116334-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003755.5(EIF3G):c.596-260T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 559,972 control chromosomes in the GnomAD database, including 102,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.59 ( 26383 hom., cov: 32)

Exomes 𝑓: 0.61 ( 76421 hom. )

Consequence

EIF3G
NM_003755.5 intron

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: -3.00

Publications

9 publications found

Variant links:

Genes affected

EIF3G (HGNC:3274): (eukaryotic translation initiation factor 3 subunit G) This gene encodes a core subunit of the eukaryotic translation initiation factor 3 (eIF3) complex, which is required for initiation of protein translation. An N-terminal caspase cleavage product of the encoded protein may stimulate degradation of DNA. A mutation in this gene is associated with narcolepsy. [provided by RefSeq, Jul 2016]

EIF3G links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3G	NM_003755.5 link	c.596-260T>C		intron_variant	Intron 7 of 10	ENST00000253108.9	NP_003746.2	O75821

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3G	ENST00000253108.9 link	c.596-260T>C		intron_variant	Intron 7 of 10	1	NM_003755.5	ENSP00000253108.3		O75821

Frequencies

GnomAD3 genomes

AF:

0.585

AC:

88846

AN:

151898

Hom.:

26352

Cov.:

show subpopulations

Gnomad AFR

AF:

0.518

Gnomad AMI

AF:

0.516

Gnomad AMR

AF:

0.664

Gnomad ASJ

AF:

0.571

Gnomad EAS

AF:

0.724

Gnomad SAS

AF:

0.698

Gnomad FIN

AF:

0.619

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.585

Gnomad OTH

AF:

0.612

GnomAD4 exome

AF:

0.609

AC:

248506

AN:

407954

Hom.:

76421

Cov.:

AF XY:

0.613

AC XY:

131099

AN XY:

213728

show subpopulations

African (AFR)

AF:

0.513

AC:

5892

AN:

11488

American (AMR)

AF:

0.688

AC:

10561

AN:

15342

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

7210

AN:

12834

East Asian (EAS)

AF:

0.715

AC:

20048

AN:

28024

South Asian (SAS)

AF:

0.682

AC:

28519

AN:

41824

European-Finnish (FIN)

AF:

0.614

AC:

16662

AN:

27138

Middle Eastern (MID)

AF:

0.545

AC:

1024

AN:

1878

European-Non Finnish (NFE)

AF:

0.587

AC:

144238

AN:

245560

Other (OTH)

AF:

0.601

AC:

14352

AN:

23866

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

4487

8974

13460

17947

22434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

742

1484

2226

2968

3710

<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:

0.585

AC:

88935

AN:

152018

Hom.:

26383

Cov.:

AF XY:

0.591

AC XY:

43902

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.518

AC:

21494

AN:

41456

American (AMR)

AF:

0.663

AC:

10125

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

1980

AN:

3468

East Asian (EAS)

AF:

0.725

AC:

3744

AN:

5164

South Asian (SAS)

AF:

0.699

AC:

3373

AN:

4824

European-Finnish (FIN)

AF:

0.619

AC:

6540

AN:

10566

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.585

AC:

39758

AN:

67964

Other (OTH)

AF:

0.614

AC:

1294

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1900

3800

5699

7599

9499

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.585

Hom.:

9762

Bravo

AF:

0.587

Asia WGS

AF:

0.699

AC:

2428

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Cataplexy and narcolepsy

Other:1

Dec 10, 2014

Center for Narcolepsy, Stanford University

Significance:association

Review Status:no assertion criteria provided

Collection Method:case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.092

(source)

DANN

Benign

0.076

PhyloP100

-3.0

PromoterAI

0.031

Neutral

(source)

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