1-21003621-G-C

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.78
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]
RPS15AP6 (HGNC:35657): (ribosomal protein S15a pseudogene 6)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 60 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EIF4G3NM_001391906.1 linkc.-66-813C>G intron_variant Intron 4 of 36 ENST00000602326.6 NP_001378835.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EIF4G3ENST00000602326.6 linkc.-66-813C>G intron_variant Intron 4 of 36 1 NM_001391906.1 ENSP00000473510.2 A0A8J9G7U8
EIF4G3ENST00000356916.7 linkc.-66-813C>G intron_variant Intron 6 of 14 1 ENSP00000349386.3 O43432-2

Frequencies

GnomAD3 genomes
AF:
0.0205
AC:
3121
AN:
152090
Hom.:
60
Cov.:
32
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.:
45
Cov.:
0
AF XY:
0.0194
AC XY:
1989
AN XY:
102662
show subpopulations
Gnomad4 AFR exome
AF:
0.00569
Gnomad4 AMR exome
AF:
0.00569
Gnomad4 ASJ exome
AF:
0.0170
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00521
Gnomad4 FIN exome
AF:
0.0454
Gnomad4 NFE exome
AF:
0.0258
Gnomad4 OTH exome
AF:
0.0266
GnomAD4 genome
AF:
0.0205
AC:
3117
AN:
152210
Hom.:
60
Cov.:
32
AF XY:
0.0216
AC XY:
1604
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.00489
Gnomad4 AMR
AF:
0.0162
Gnomad4 ASJ
AF:
0.0262
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00498
Gnomad4 FIN
AF:
0.0637
Gnomad4 NFE
AF:
0.0265
Gnomad4 OTH
AF:
0.0209
Alfa
AF:
0.0133
Hom.:
5
Bravo
AF:
0.0168
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
CADD
Benign
11
DANN
Benign
0.77

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10493005; hg19: chr1-21330114; API