Variant rs1879244 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.3954-64C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,612,336 control chromosomes in the GnomAD database, including 456,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 49388 hom., cov: 31)

Exomes 𝑓: 0.75 ( 407544 hom. )

Consequence

EIF4G1
NM_198241.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.132

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 3-184328567-C-T is Benign according to our data. Variant chr3-184328567-C-T is described in ClinVar as [Benign]. Clinvar id is 1271491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.945 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.3954-64C>T		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.3954-64C>T		intron_variant		1	NM_198241.3	ENSP00000316879	A2	Q04637-1

Frequencies

GnomAD3 genomes

AF:

0.798

AC:

121348

AN:

151998

Hom.:

49328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.953

Gnomad AMI

AF:

0.491

Gnomad AMR

AF:

0.808

Gnomad ASJ

AF:

0.825

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.663

Gnomad FIN

AF:

0.688

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.743

Gnomad OTH

AF:

0.818

GnomAD4 exome

AF:

0.745

AC:

1088202

AN:

1460220

Hom.:

407544

Cov.:

AF XY:

0.742

AC XY:

538847

AN XY:

726490

show subpopulations

Gnomad4 AFR exome

AF:

0.961

Gnomad4 AMR exome

AF:

0.821

Gnomad4 ASJ exome

AF:

0.828

Gnomad4 EAS exome

AF:

0.623

Gnomad4 SAS exome

AF:

0.668

Gnomad4 FIN exome

AF:

0.697

Gnomad4 NFE exome

AF:

0.745

Gnomad4 OTH exome

AF:

0.759

GnomAD4 genome

AF:

0.798

AC:

121458

AN:

152116

Hom.:

49388

Cov.:

AF XY:

0.790

AC XY:

58723

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.953

Gnomad4 AMR

AF:

0.809

Gnomad4 ASJ

AF:

0.825

Gnomad4 EAS

AF:

0.635

Gnomad4 SAS

AF:

0.663

Gnomad4 FIN

AF:

0.688

Gnomad4 NFE

AF:

0.743

Gnomad4 OTH

AF:

0.810

Alfa

AF:

0.773

Hom.:

6218

Bravo

AF:

0.818

Asia WGS

AF:

0.674

AC:

2347

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 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.84

DANN

Benign

0.24

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