2-232561816-C-T

Variant names:

• chr2-232561816-C-T
• rs1656402
• NM_004846.4:c.271-2431C>T

Variant summary

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

The NM_004846.4(EIF4E2):​c.271-2431C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 151,960 control chromosomes in the GnomAD database, including 7,630 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 (7630 hom., cov: 32)
• Consequence: EIF4E2 NM_004846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826
• Publications: 24 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004846.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E2	NM_004846.4	MANE Select	c.271-2431C>T		intron	N/A	NP_004837.1	O60573-1
	EIF4E2	NM_001330202.2		c.256-2431C>T		intron	N/A	NP_001317131.1
	EIF4E2	NM_001282958.2		c.271-2431C>T		intron	N/A	NP_001269887.1	B8ZZ50

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E2	ENST00000258416.8	TSL:1 MANE Select	c.271-2431C>T		intron	N/A	ENSP00000258416.3	O60573-1
	EIF4E2	ENST00000409098.5	TSL:1	c.271-2431C>T		intron	N/A	ENSP00000386996.1	O60573-2
	EIF4E2	ENST00000931066.1		c.262-2431C>T		intron	N/A	ENSP00000601125.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46380 AN: 151844 Hom.: 7612 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.306 AC: 46444 AN: 151960 Hom.: 7630 Cov.: 32 AF XY: 0.305 AC XY: 22687 AN XY: 74282

African (AFR) AF: 0.399 AC: 16509 AN: 41426

American (AMR) AF: 0.414 AC: 6320 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3464

East Asian (EAS) AF: 0.281 AC: 1451 AN: 5172

South Asian (SAS) AF: 0.238 AC: 1145 AN: 4820

European-Finnish (FIN) AF: 0.205 AC: 2161 AN: 10532

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16774 AN: 67976

Other (OTH) AF: 0.320 AC: 673 AN: 2106

Alfa AF: 0.271 Hom.: 24814

Bravo AF: 0.327

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.39
PhyloP100		-0.83
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: rs1656402; hg19: chr2-233426526; COSMIC: COSV51471183;