chr2-232553262-A-G

Variant names:

• chr2-232553262-A-G
• rs10498262
• NM_004846.4:c.20+2518A>G

Variant summary

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

The NM_004846.4(EIF4E2):​c.20+2518A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 148,856 control chromosomes in the GnomAD database, including 152 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 0.034 (152 hom., cov: 32)
• Consequence: EIF4E2 NM_004846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607
• Publications: 0 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4E2	NM_004846.4	c.20+2518A>G		intron_variant	Intron 1 of 6	ENST00000258416.8	NP_004837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4E2	ENST00000258416.8	c.20+2518A>G		intron_variant	Intron 1 of 6	1	NM_004846.4	ENSP00000258416.3

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5031 AN: 148736 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.0178

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.0440

Gnomad EAS AF: 0.0734

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.000288

Gnomad MID AF: 0.0700

Gnomad NFE AF: 0.00522

Gnomad OTH AF: 0.0376

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

GnomAD4 genome AF: 0.0338 AC: 5034 AN: 148856 Hom.: 152 Cov.: 32 AF XY: 0.0341 AC XY: 2489 AN XY: 72912

African (AFR) AF: 0.0750 AC: 3054 AN: 40726

American (AMR) AF: 0.0536 AC: 803 AN: 14994

Ashkenazi Jewish (ASJ) AF: 0.0440 AC: 149 AN: 3386

East Asian (EAS) AF: 0.0738 AC: 374 AN: 5070

South Asian (SAS) AF: 0.0405 AC: 191 AN: 4718

European-Finnish (FIN) AF: 0.000288 AC: 3 AN: 10432

Middle Eastern (MID) AF: 0.0750 AC: 21 AN: 280

European-Non Finnish (NFE) AF: 0.00522 AC: 346 AN: 66282

Other (OTH) AF: 0.0372 AC: 77 AN: 2070

Alfa AF: 0.0267 Hom.: 49

Bravo AF: 0.0387

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.69
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10498262; hg19: chr2-233417972;