rs10498262

Positions:

• chr2-232553262-A-G

Variant summary

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

The NM_004846.4(EIF4E2):​c.20+2518A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 148,856 control chromosomes in the GnomAD database, including 152 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 0.034 (152 hom., cov: 32)
• Consequence: EIF4E2 NM_004846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607

Genes affected

EIF4E2 (HGNC:3293): (eukaryotic translation initiation factor 4E family member 2) Enables ubiquitin protein ligase binding activity. Involved in positive regulation of miRNA mediated inhibition of translation. Acts upstream of or within negative regulation of translation. Located in P-body. Part of mRNA cap binding activity complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4E2	NM_004846.4	c.20+2518A>G		intron_variant		ENST00000258416.8	NP_004837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4E2	ENST00000258416.8	c.20+2518A>G		intron_variant		1	NM_004846.4	ENSP00000258416.3

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5031 AN: 148736 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.0178

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.0440

Gnomad EAS AF: 0.0734

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.000288

Gnomad MID AF: 0.0700

Gnomad NFE AF: 0.00522

Gnomad OTH AF: 0.0376

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

GnomAD4 genome AF: 0.0338 AC: 5034 AN: 148856 Hom.: 152 Cov.: 32 AF XY: 0.0341 AC XY: 2489 AN XY: 72912

Gnomad4 AFR AF: 0.0750

Gnomad4 AMR AF: 0.0536

Gnomad4 ASJ AF: 0.0440

Gnomad4 EAS AF: 0.0738

Gnomad4 SAS AF: 0.0405

Gnomad4 FIN AF: 0.000288

Gnomad4 NFE AF: 0.00522

Gnomad4 OTH AF: 0.0372

Alfa AF: 0.0259 Hom.: 28

Bravo AF: 0.0387

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.69

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: rs10498262; hg19: chr2-233417972;