rs13109000

Positions:

• chr4-98894380-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001968.5(EIF4E):​c.126-3048A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.04 in 151,844 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.040 (4 hom., cov: 34)
• Consequence: EIF4E NM_001968.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413

Genes affected

EIF4E (HGNC:3287): (eukaryotic translation initiation factor 4E) The protein encoded by this gene is a component of the eukaryotic translation initiation factor 4F complex, which recognizes the 7-methylguanosine cap structure at the 5' end of messenger RNAs. The encoded protein aids in translation initiation by recruiting ribosomes to the 5'-cap structure. Association of this protein with the 4F complex is the rate-limiting step in translation initiation. This gene acts as a proto-oncogene, and its expression and activation is associated with transformation and tumorigenesis. Several pseudogenes of this gene are found on other chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4E	NM_001968.5	c.126-3048A>G		intron_variant		ENST00000450253.7	NP_001959.1
EIF4E	NM_001130679.3	c.126-3048A>G		intron_variant			NP_001124151.1
EIF4E	NM_001331017.2	c.210-3048A>G		intron_variant			NP_001317946.1
EIF4E	NM_001130678.4	c.186-3048A>G		intron_variant			NP_001124150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4E	ENST00000450253.7	c.126-3048A>G		intron_variant		1	NM_001968.5	ENSP00000389624.2

Frequencies

GnomAD3 genomes AF: 0.0401 AC: 6079 AN: 151726 Hom.: 4 Cov.: 34

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.0355

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0204

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0638

Gnomad OTH AF: 0.0485

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0400 AC: 6077 AN: 151844 Hom.: 4 Cov.: 34 AF XY: 0.0372 AC XY: 2765 AN XY: 74276

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.0465

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.0204

Gnomad4 NFE AF: 0.0639

Gnomad4 OTH AF: 0.0480

Alfa AF: 0.0489 Hom.: 3

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.7
DANN	Benign	0.61

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

Other links and lift over

dbSNP: rs13109000; hg19: chr4-99815531;