rs1656402

chr2-232561816-C-T

Variant summary

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

The NM_004846.4(EIF4E2):c.271-2431C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 151,960 control chromosomes in the GnomAD database, including 7,630 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 0.31 (7630 hom., cov: 32)
• Consequence: EIF4E2 NM_004846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4E2	NM_004846.4	c.271-2431C>T		intron_variant		ENST00000258416.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4E2	ENST00000258416.8	c.271-2431C>T		intron_variant		1	NM_004846.4

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46380 AN: 151844 Hom.: 7612 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.306 AC: 46444 AN: 151960 Hom.: 7630 Cov.: 32 AF XY: 0.305 AC XY: 22687 AN XY: 74282

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.320

Alfa AF: 0.264 Hom.: 10805

Bravo AF: 0.327

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.1
Dann	Benign	0.39

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: rs1656402; hg19: chr2-233426526; COSMIC: COSV51471183; COSMIC: COSV51471183;