Variant rs4912537 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.698-101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,528,668 control chromosomes in the GnomAD database, including 39,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3201 hom., cov: 32)

Exomes 𝑓: 0.23 ( 36395 hom. )

Consequence

EIF4G1
NM_198241.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.30

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 3-184321181-C-T is Benign according to our data. Variant chr3-184321181-C-T is described in ClinVar as [Benign]. Clinvar id is 1272665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 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.698-101C>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.698-101C>T		intron_variant		1	NM_198241.3	ENSP00000316879	A2	Q04637-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30367

AN:

151860

Hom.:

3200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.0881

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.185

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.200

GnomAD4 exome

AF:

0.227

AC:

312300

AN:

1376690

Hom.:

36395

Cov.:

AF XY:

0.225

AC XY:

155079

AN XY:

689132

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.193

Gnomad4 EAS exome

AF:

0.186

Gnomad4 SAS exome

AF:

0.152

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.237

Gnomad4 OTH exome

AF:

0.205

GnomAD4 genome

AF:

0.200

AC:

30379

AN:

151978

Hom.:

3201

Cov.:

AF XY:

0.201

AC XY:

14910

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.147

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.185

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.303

Gnomad4 NFE

AF:

0.229

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.220

Hom.:

7527

Bravo

AF:

0.190

Asia WGS

AF:

0.137

AC:

477

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

0.074

DANN

Benign

0.32

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