rs7078987

Positions:

• chr10-70413236-A-G
• chr10-70413236-A-T

Variant summary

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

The NM_004096.5(EIF4EBP2):​c.146-6678A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,984 control chromosomes in the GnomAD database, including 11,296 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 0.35 (11296 hom., cov: 31)
• Consequence: EIF4EBP2 NM_004096.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

Genes affected

EIF4EBP2 (HGNC:3289): (eukaryotic translation initiation factor 4E binding protein 2) This gene encodes a member of the eukaryotic translation initiation factor 4E binding protein family. The gene products of this family bind eIF4E and inhibit translation initiation. However, insulin and other growth factors can release this inhibition via a phosphorylation-dependent disruption of their binding to eIF4E. Regulation of protein production through these gene products have been implicated in cell proliferation, cell differentiation and viral infection. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4EBP2	NM_004096.5	c.146-6678A>G		intron_variant		ENST00000373218.5	NP_004087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4EBP2	ENST00000373218.5	c.146-6678A>G		intron_variant		1	NM_004096.5	ENSP00000362314	P1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53556 AN: 151868 Hom.: 11291 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.352 AC: 53557 AN: 151984 Hom.: 11296 Cov.: 31 AF XY: 0.352 AC XY: 26140 AN XY: 74266

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.375

Alfa AF: 0.429 Hom.: 19171

Bravo AF: 0.344

Asia WGS AF: 0.388 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.79

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: rs7078987; hg19: chr10-72172992;