rs1550099

Positions:

• chr2-232563437-A-G
• chr2-232563437-A-T

Variant summary

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

The NM_004846.4(EIF4E2):​c.271-810A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,388 control chromosomes in the GnomAD database, including 5,654 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 0.27 (5654 hom., cov: 30)
• Consequence: EIF4E2 NM_004846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4E2	NM_004846.4	c.271-810A>G		intron_variant		ENST00000258416.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4E2	ENST00000258416.8	c.271-810A>G		intron_variant		1	NM_004846.4

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40413 AN: 151272 Hom.: 5641 Cov.: 30

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.221

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.267 AC: 40470 AN: 151388 Hom.: 5654 Cov.: 30 AF XY: 0.267 AC XY: 19751 AN XY: 73926

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.282

Alfa AF: 0.273 Hom.: 1280

Bravo AF: 0.285

Asia WGS AF: 0.245 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.74
DANN	Benign	0.35

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: rs1550099; hg19: chr2-233428147;