rs3791723

chr2-232555133-G-Achr2-232555133-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.21-1283G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 152,240 control chromosomes in the GnomAD database, including 160 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 0.033 (160 hom., cov: 32)
• Consequence: EIF4E2 NM_004846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4E2	NM_004846.4	c.21-1283G>A		intron_variant		ENST00000258416.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4E2	ENST00000258416.8	c.21-1283G>A		intron_variant		1	NM_004846.4

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5071 AN: 152122 Hom.: 160 Cov.: 32

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.0436

Gnomad EAS AF: 0.0736

Gnomad SAS AF: 0.0404

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.00506

Gnomad OTH AF: 0.0364

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

GnomAD4 genome AF: 0.0333 AC: 5074 AN: 152240 Hom.: 160 Cov.: 32 AF XY: 0.0337 AC XY: 2506 AN XY: 74434

Gnomad4 AFR AF: 0.0743

Gnomad4 AMR AF: 0.0524

Gnomad4 ASJ AF: 0.0436

Gnomad4 EAS AF: 0.0740

Gnomad4 SAS AF: 0.0406

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00506

Gnomad4 OTH AF: 0.0361

Alfa AF: 0.0250 Hom.: 11

Bravo AF: 0.0386

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	7.3
Dann	Benign	0.78

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: rs3791723; hg19: chr2-233419843;