Variant 3-184315558-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198241.3(EIF4G1):c.-35+13T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 757,412 control chromosomes in the GnomAD database, including 393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 171 hom., cov: 32)

Exomes 𝑓: 0.020 ( 222 hom. )

Consequence

EIF4G1
NM_198241.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.585

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 links:

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=-0.73).

BP6

Variant 3-184315558-T-A is Benign according to our data. Variant chr3-184315558-T-A is described in ClinVar as [Benign]. Clinvar id is 1258758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-184315558-T-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4G1	NM_198241.3 linkuse as main transcript	c.-35+13T>A		intron_variant		ENST00000346169.7	NP_937884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4G1	ENST00000346169.7 linkuse as main transcript	c.-35+13T>A		intron_variant		1	NM_198241.3	ENSP00000316879	A2	Q04637-1

Frequencies

GnomAD3 genomes

AF:

0.0383

AC:

5823

AN:

152028

Hom.:

172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0826

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0210

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0340

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0237

Gnomad OTH

AF:

0.0340

GnomAD3 exomes

AF:

0.0201

AC:

4708

AN:

234802

Hom.:

104

AF XY:

0.0188

AC XY:

2440

AN XY:

129522

show subpopulations

Gnomad AFR exome

AF:

0.0838

Gnomad AMR exome

AF:

0.00839

Gnomad ASJ exome

AF:

0.00275

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00253

Gnomad FIN exome

AF:

0.0329

Gnomad NFE exome

AF:

0.0235

Gnomad OTH exome

AF:

0.0186

GnomAD4 exome

AF:

0.0200

AC:

12125

AN:

605266

Hom.:

222

Cov.:

AF XY:

0.0187

AC XY:

6168

AN XY:

330654

show subpopulations

Gnomad4 AFR exome

AF:

0.0854

Gnomad4 AMR exome

AF:

0.0106

Gnomad4 ASJ exome

AF:

0.00292

Gnomad4 EAS exome

AF:

0.0000286

Gnomad4 SAS exome

AF:

0.00217

Gnomad4 FIN exome

AF:

0.0322

Gnomad4 NFE exome

AF:

0.0231

Gnomad4 OTH exome

AF:

0.0208

GnomAD4 genome

AF:

0.0383

AC:

5831

AN:

152146

Hom.:

171

Cov.:

AF XY:

0.0364

AC XY:

2707

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0825

Gnomad4 AMR

AF:

0.0210

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.0340

Gnomad4 NFE

AF:

0.0237

Gnomad4 OTH

AF:

0.0342

Alfa

AF:

0.0244

Hom.:

Bravo

AF:

0.0403

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.4

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over