2-232554210-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.21-2206G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,044 control chromosomes in the GnomAD database, including 28,433 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 0.61 (28433 hom., cov: 32)
• Consequence: EIF4E2 NM_004846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4E2	NM_004846.4	c.21-2206G>T		intron_variant		ENST00000258416.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4E2	ENST00000258416.8	c.21-2206G>T		intron_variant		1	NM_004846.4

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91896 AN: 151926 Hom.: 28388 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.605 AC: 92004 AN: 152044 Hom.: 28433 Cov.: 32 AF XY: 0.602 AC XY: 44763 AN XY: 74314

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.611

Alfa AF: 0.571 Hom.: 24212

Bravo AF: 0.629

Asia WGS AF: 0.663 AC: 2305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.30
Dann	Benign	0.22

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: rs1190449; hg19: chr2-233418920;