rs2293605

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000346169.7(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
ENST00000346169.7 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.672
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 518345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-184326645-C-T is described in Lovd as [Benign].
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/exons MANE Protein UniProt
EIF4G1NM_198241.3 linkuse as main transcriptc.3325+16C>T intron_variant ENST00000346169.7 NP_937884.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EIF4G1ENST00000346169.7 linkuse as main transcriptc.3325+16C>T intron_variant 1 NM_198241.3 ENSP00000316879 A2Q04637-1

Frequencies

GnomAD3 genomes
AF:
0.0897
AC:
13653
AN:
152170
Hom.:
811
Cov.:
33
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
GnomAD3 exomes
AF:
0.106
AC:
26125
AN:
245644
Hom.:
1624
AF XY:
0.109
AC XY:
14492
AN XY:
133300
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 SAS exome
AF:
0.105
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.:
32
AF XY:
0.116
AC XY:
83893
AN XY:
723818
show subpopulations
Gnomad4 AFR exome
AF:
0.0178
Gnomad4 AMR exome
AF:
0.108
Gnomad4 ASJ exome
AF:
0.105
Gnomad4 EAS exome
AF:
0.0179
Gnomad4 SAS exome
AF:
0.105
Gnomad4 FIN exome
AF:
0.165
Gnomad4 NFE exome
AF:
0.122
Gnomad4 OTH exome
AF:
0.101
GnomAD4 genome
AF:
0.0896
AC:
13648
AN:
152288
Hom.:
810
Cov.:
33
AF XY:
0.0908
AC XY:
6761
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0214
Gnomad4 AMR
AF:
0.0893
Gnomad4 ASJ
AF:
0.0983
Gnomad4 EAS
AF:
0.0266
Gnomad4 SAS
AF:
0.106
Gnomad4 FIN
AF:
0.165
Gnomad4 NFE
AF:
0.124
Gnomad4 OTH
AF:
0.0863
Alfa
AF:
0.111
Hom.:
580
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
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, Amsterdam University Medical Center-- -
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 19, 2021- -
Parkinson disease 18, autosomal dominant, susceptibility to Benign:1
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.13
DANN
Benign
0.52
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs2293605; hg19: chr3-184044433; API