rs1190452

Positions:

• chr2-232552842-G-A
• chr2-232552842-G-C
• chr2-232552842-G-T

Variant summary

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

The NM_004846.4(EIF4E2):​c.20+2098G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,094 control chromosomes in the GnomAD database, including 41,372 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 0.73 (41372 hom., cov: 33)
• Consequence: EIF4E2 NM_004846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4E2	NM_004846.4	c.20+2098G>A		intron_variant		ENST00000258416.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4E2	ENST00000258416.8	c.20+2098G>A		intron_variant		1	NM_004846.4

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111660 AN: 151980 Hom.: 41329 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.735 AC: 111755 AN: 152094 Hom.: 41372 Cov.: 33 AF XY: 0.733 AC XY: 54479 AN XY: 74344

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.769

Alfa AF: 0.728 Hom.: 64493

Bravo AF: 0.750

Asia WGS AF: 0.747 AC: 2599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.78
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: rs1190452; hg19: chr2-233417552;