2-232554210-G-T

Variant names:

• chr2-232554210-G-T
• rs1190449
• NM_004846.4:c.21-2206G>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.21-2206G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,044 control chromosomes in the GnomAD database, including 28,433 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 0.61 (28433 hom., cov: 32)
• Consequence: EIF4E2 NM_004846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.694 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.21-2206G>T		intron	N/A	NP_004837.1	O60573-1
	EIF4E2	NM_001330202.2		c.6-2206G>T		intron	N/A	NP_001317131.1
	EIF4E2	NM_001282958.2		c.21-2206G>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.21-2206G>T		intron	N/A	ENSP00000258416.3	O60573-1
	EIF4E2	ENST00000409098.5	TSL:1	c.21-2206G>T		intron	N/A	ENSP00000386996.1	O60573-2
	EIF4E2	ENST00000931066.1		c.12-2206G>T		intron	N/A	ENSP00000601125.1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91896 AN: 151926 Hom.: 28388 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.605 AC: 92004 AN: 152044 Hom.: 28433 Cov.: 32 AF XY: 0.602 AC XY: 44763 AN XY: 74314

African (AFR) AF: 0.701 AC: 29073 AN: 41472

American (AMR) AF: 0.704 AC: 10740 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1984 AN: 3466

East Asian (EAS) AF: 0.573 AC: 2958 AN: 5166

South Asian (SAS) AF: 0.608 AC: 2932 AN: 4820

European-Finnish (FIN) AF: 0.505 AC: 5338 AN: 10574

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36857 AN: 67970

Other (OTH) AF: 0.611 AC: 1290 AN: 2112

Alfa AF: 0.579 Hom.: 32528

Bravo AF: 0.629

Asia WGS AF: 0.663 AC: 2305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.22
PhyloP100		-0.79
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: rs1190449; hg19: chr2-233418920;