2-232573207-G-T

Variant names:

• chr2-232573207-G-T
• rs6749955
• ENST00000409098.5:c.665+5993G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282958.2(EIF4E2):​c.666-1056G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,076 control chromosomes in the GnomAD database, including 37,186 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 0.69 (37186 hom., cov: 32)
• Consequence: EIF4E2 NM_001282958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282958.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E2	NM_001282958.2		c.666-1056G>T		intron	N/A	NP_001269887.1
	EIF4E2	NM_001276336.2		c.665+5993G>T		intron	N/A	NP_001263265.1
	EIF4E2	NM_001330203.2		c.531-1056G>T		intron	N/A	NP_001317132.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E2	ENST00000409098.5	TSL:1	c.665+5993G>T		intron	N/A	ENSP00000386996.1
	EIF4E2	ENST00000409514.5	TSL:5	c.666-1056G>T		intron	N/A	ENSP00000387336.1
	EIF4E2	ENST00000687222.1		c.531-1056G>T		intron	N/A	ENSP00000508671.1

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105543 AN: 151958 Hom.: 37174 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.694 AC: 105596 AN: 152076 Hom.: 37186 Cov.: 32 AF XY: 0.695 AC XY: 51683 AN XY: 74362

African (AFR) AF: 0.600 AC: 24864 AN: 41444

American (AMR) AF: 0.590 AC: 9016 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2427 AN: 3468

East Asian (EAS) AF: 0.718 AC: 3710 AN: 5170

South Asian (SAS) AF: 0.762 AC: 3676 AN: 4822

European-Finnish (FIN) AF: 0.795 AC: 8411 AN: 10580

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51220 AN: 67992

Other (OTH) AF: 0.682 AC: 1438 AN: 2108

Alfa AF: 0.733 Hom.: 22278

Bravo AF: 0.673

Asia WGS AF: 0.710 AC: 2467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.30
DANN	Benign	0.41
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6749955; hg19: chr2-233437917;