rs1656400

Variant names:

• chr2-232563073-G-A
• rs1656400
• NM_004846.4:c.271-1174G>A

Variant summary

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

The NM_004846.4(EIF4E2):​c.271-1174G>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
• Publications: 5 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=-0.99).
• 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 rank	MANE	Protein	UniProt
EIF4E2	NM_004846.4	c.271-1174G>A		intron_variant	Intron 3 of 6	ENST00000258416.8	NP_004837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4E2	ENST00000258416.8	c.271-1174G>A		intron_variant	Intron 3 of 6	1	NM_004846.4	ENSP00000258416.3

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

African (AFR) AF: 0.398 AC: 16494 AN: 41448

American (AMR) AF: 0.413 AC: 6311 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1039 AN: 3468

East Asian (EAS) AF: 0.279 AC: 1445 AN: 5178

South Asian (SAS) AF: 0.238 AC: 1145 AN: 4818

European-Finnish (FIN) AF: 0.206 AC: 2176 AN: 10576

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

European-Non Finnish (NFE) AF: 0.247 AC: 16763 AN: 67960

Other (OTH) AF: 0.318 AC: 672 AN: 2110

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
PhyloP100		-1.7
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: rs1656400; hg19: chr2-233427783;