2-232573207-G-T

Position:

• chr2-232573207-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

EIF4E2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4E2	NM_001282958.2	c.666-1056G>T		intron_variant			NP_001269887.1
EIF4E2	NM_001276336.2	c.665+5993G>T		intron_variant			NP_001263265.1
EIF4E2	NM_001330203.2	c.531-1056G>T		intron_variant			NP_001317132.1
EIF4E2	NM_001276337.2	c.530+5993G>T		intron_variant			NP_001263266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4E2	ENST00000409098.5	c.665+5993G>T		intron_variant		1		ENSP00000386996.1
EIF4E2	ENST00000409514.5	c.666-1056G>T		intron_variant		5		ENSP00000387336.1
EIF4E2	ENST00000687222.1	c.531-1056G>T		intron_variant				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

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.682

Alfa AF: 0.732 Hom.: 20130

Bravo AF: 0.673

Asia WGS AF: 0.710 AC: 2467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.30
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6749955; hg19: chr2-233437917;