Genetic Variant EIF4G3:c.-66-813C>G (chr1-21003621-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001391906.1(EIF4G3):c.-66-813C>G variant causes a intron change. The variant allele was found at a frequency of 0.0205 in 326,596 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.020 ( 60 hom., cov: 32)

Exomes 𝑓: 0.020 ( 45 hom. )

Consequence

EIF4G3
NM_001391906.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.78

Publications

0 publications found

Variant links:

Genes affected

EIF4G3 (HGNC:3298): (eukaryotic translation initiation factor 4 gamma 3) The protein encoded by this gene is thought to be part of the eIF4F protein complex, which is involved in mRNA cap recognition and transport of mRNAs to the ribosome. Interestingly, a microRNA (miR-520c-3p) has been found that negatively regulates synthesis of the encoded protein, and this leads to a global decrease in protein translation and cell proliferation. Therefore, this protein is a key component of the anti-tumor activity of miR-520c-3p. [provided by RefSeq, May 2016]

EIF4G3 links:

RPS15AP6 (HGNC:35657): (ribosomal protein S15a pseudogene 6)

RPS15AP6 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001391906.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.52).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0205 (3117/152210) while in subpopulation NFE AF = 0.0265 (1805/68010). AF 95% confidence interval is 0.0255. There are 60 homozygotes in GnomAd4. There are 1604 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 60 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001391906.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EIF4G3	NM_001391906.1	MANE Select	c.-66-813C>G	intron	N/A	NP_001378835.1	A0A8J9G7U8
EIF4G3	NM_001391907.1		c.-66-813C>G	intron	N/A	NP_001378836.1
EIF4G3	NM_001438678.1		c.-66-813C>G	intron	N/A	NP_001425607.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EIF4G3	ENST00000602326.6	TSL:1 MANE Select	c.-66-813C>G	intron	N/A	ENSP00000473510.2	A0A8J9G7U8
EIF4G3	ENST00000400422.6	TSL:1	c.-66-813C>G	intron	N/A	ENSP00000383274.2	A0A0A0MSA7
EIF4G3	ENST00000356916.7	TSL:1	c.-66-813C>G	intron	N/A	ENSP00000349386.3	O43432-2

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3121

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00490

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.0262

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0637

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0266

Gnomad OTH

AF:

0.0211

GnomAD4 exome

AF:

0.0205

AC:

3569

AN:

174386

Hom.:

Cov.:

AF XY:

0.0194

AC XY:

1989

AN XY:

102662

show subpopulations

African (AFR)

AF:

0.00569

AC:

AN:

3514

American (AMR)

AF:

0.00569

AC:

AN:

12650

Ashkenazi Jewish (ASJ)

AF:

0.0170

AC:

AN:

3410

East Asian (EAS)

AF:

0.00

AC:

AN:

5730

South Asian (SAS)

AF:

0.00521

AC:

156

AN:

29950

European-Finnish (FIN)

AF:

0.0454

AC:

447

AN:

9854

Middle Eastern (MID)

AF:

0.0110

AC:

AN:

544

European-Non Finnish (NFE)

AF:

0.0258

AC:

2593

AN:

100588

Other (OTH)

AF:

0.0266

AC:

217

AN:

8146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

142

284

426

568

710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0205

AC:

3117

AN:

152210

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1604

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.00489

AC:

203

AN:

41548

American (AMR)

AF:

0.0162

AC:

248

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0262

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00498

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0637

AC:

674

AN:

10578

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0265

AC:

1805

AN:

68010

Other (OTH)

AF:

0.0209

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

145

289

434

578

723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0133

Hom.:

Bravo

AF:

0.0168

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

6.8

Mutation Taster

=99/1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over