Variant 3-184321086-A-T 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.697+93A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,524,358 control chromosomes in the GnomAD database, including 59,374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10901 hom., cov: 32)

Exomes 𝑓: 0.25 ( 48473 hom. )

Consequence

EIF4G1
NM_198241.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.602

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=-0.88).

BP6

Variant 3-184321086-A-T is Benign according to our data. Variant chr3-184321086-A-T is described in ClinVar as [Benign]. Clinvar id is 1260000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4G1	NM_198241.3 linkuse as main transcript	c.697+93A>T		intron_variant		ENST00000346169.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4G1	ENST00000346169.7 linkuse as main transcript	c.697+93A>T		intron_variant		1	NM_198241.3	A2	Q04637-1

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53213

AN:

151950

Hom.:

10886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.549

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.430

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.384

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.359

GnomAD4 exome

AF:

0.255

AC:

349569

AN:

1372290

Hom.:

48473

Cov.:

AF XY:

0.252

AC XY:

171646

AN XY:

680192

show subpopulations

Gnomad4 AFR exome

AF:

0.553

Gnomad4 AMR exome

AF:

0.490

Gnomad4 ASJ exome

AF:

0.388

Gnomad4 EAS exome

AF:

0.399

Gnomad4 SAS exome

AF:

0.230

Gnomad4 FIN exome

AF:

0.226

Gnomad4 NFE exome

AF:

0.230

Gnomad4 OTH exome

AF:

0.298

GnomAD4 genome

AF:

0.350

AC:

53270

AN:

152068

Hom.:

10901

Cov.:

AF XY:

0.350

AC XY:

25995

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.549

Gnomad4 AMR

AF:

0.431

Gnomad4 ASJ

AF:

0.395

Gnomad4 EAS

AF:

0.385

Gnomad4 SAS

AF:

0.228

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.238

Gnomad4 OTH

AF:

0.355

Alfa

AF:

0.301

Hom.:

1025

Bravo

AF:

0.381

Asia WGS

AF:

0.329

AC:

1146

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.6

DANN

Benign

0.59

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