rs1656400

Positions:

• chr2-232563073-G-A

Variant summary

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

The NM_004846.4(EIF4E2):​c.271-1174G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,036 control chromosomes in the GnomAD database, including 7,618 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 0.31 (7618 hom., cov: 32)
• Consequence: EIF4E2 NM_004846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4E2	NM_004846.4	c.271-1174G>A		intron_variant		ENST00000258416.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4E2	ENST00000258416.8	c.271-1174G>A		intron_variant		1	NM_004846.4

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46355 AN: 151918 Hom.: 7601 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.305 AC: 46417 AN: 152036 Hom.: 7618 Cov.: 32 AF XY: 0.305 AC XY: 22664 AN XY: 74320

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.318

Alfa AF: 0.306 Hom.: 1379

Bravo AF: 0.327

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.34
DANN	Benign	0.72

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: rs1656400; hg19: chr2-233427783;