rs4699369

Positions:

• chr4-98888271-G-A

Variant summary

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

The NM_001968.5(EIF4E):​c.222-319C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,026 control chromosomes in the GnomAD database, including 3,669 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 0.19 (3669 hom., cov: 32)
• Consequence: EIF4E NM_001968.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4E	NM_001968.5	c.222-319C>T		intron_variant		ENST00000450253.7
EIF4E	NM_001130678.4	c.282-319C>T		intron_variant
EIF4E	NM_001130679.3	c.222-319C>T		intron_variant
EIF4E	NM_001331017.2	c.306-319C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4E	ENST00000450253.7	c.222-319C>T		intron_variant		1	NM_001968.5	P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28982 AN: 151908 Hom.: 3675 Cov.: 32

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.191 AC: 28982 AN: 152026 Hom.: 3669 Cov.: 32 AF XY: 0.184 AC XY: 13708 AN XY: 74312

Gnomad4 AFR AF: 0.0539

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.205

Alfa AF: 0.238 Hom.: 619

Bravo AF: 0.181

Asia WGS AF: 0.0830 AC: 291 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.58

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: rs4699369; hg19: chr4-99809422;