chr2-232555133-G-A

Variant names:

• chr2-232555133-G-A
• rs3791723
• NM_004846.4:c.21-1283G>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.21-1283G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 152,240 control chromosomes in the GnomAD database, including 160 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 0.033 (160 hom., cov: 32)
• Consequence: EIF4E2 NM_004846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 1 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0721 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E2	NM_004846.4	MANE Select	c.21-1283G>A		intron	N/A	NP_004837.1
	EIF4E2	NM_001330202.2		c.6-1283G>A		intron	N/A	NP_001317131.1
	EIF4E2	NM_001282958.2		c.21-1283G>A		intron	N/A	NP_001269887.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E2	ENST00000258416.8	TSL:1 MANE Select	c.21-1283G>A		intron	N/A	ENSP00000258416.3
	EIF4E2	ENST00000409098.5	TSL:1	c.21-1283G>A		intron	N/A	ENSP00000386996.1
	EIF4E2	ENST00000409514.5	TSL:5	c.21-1283G>A		intron	N/A	ENSP00000387336.1

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5071 AN: 152122 Hom.: 160 Cov.: 32

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.0436

Gnomad EAS AF: 0.0736

Gnomad SAS AF: 0.0404

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.00506

Gnomad OTH AF: 0.0364

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

GnomAD4 genome AF: 0.0333 AC: 5074 AN: 152240 Hom.: 160 Cov.: 32 AF XY: 0.0337 AC XY: 2506 AN XY: 74434

African (AFR) AF: 0.0743 AC: 3083 AN: 41518

American (AMR) AF: 0.0524 AC: 802 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0436 AC: 151 AN: 3466

East Asian (EAS) AF: 0.0740 AC: 383 AN: 5178

South Asian (SAS) AF: 0.0406 AC: 196 AN: 4822

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10622

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.00506 AC: 344 AN: 68028

Other (OTH) AF: 0.0361 AC: 76 AN: 2108

Alfa AF: 0.0250 Hom.: 11

Bravo AF: 0.0386

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.3
DANN	Benign	0.78
PhyloP100		-0.060
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: rs3791723; hg19: chr2-233419843;