rs11899983

chr2-232551268-T-C

Variant summary

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

The NM_004846.4(EIF4E2):c.20+524T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 471,858 control chromosomes in the GnomAD database, including 78,362 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 0.58 (25707 hom., cov: 30)
  • Exomes 𝑓: 0.57 (52655 hom.)
• Consequence: EIF4E2 NM_004846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4E2	NM_004846.4	c.20+524T>C		intron_variant		ENST00000258416.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4E2	ENST00000258416.8	c.20+524T>C		intron_variant		1	NM_004846.4

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87863 AN: 151792 Hom.: 25670 Cov.: 30

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.594

GnomAD3 exomes AF: 0.582 AC: 86881 AN: 149252 Hom.: 25601 AF XY: 0.576 AC XY: 46296 AN XY: 80388

Gnomad AFR exome AF: 0.595

Gnomad AMR exome AF: 0.696

Gnomad ASJ exome AF: 0.566

Gnomad EAS exome AF: 0.556

Gnomad SAS exome AF: 0.545

Gnomad FIN exome AF: 0.529

Gnomad NFE exome AF: 0.568

Gnomad OTH exome AF: 0.587

GnomAD4 exome AF: 0.570 AC: 182437 AN: 319946 Hom.: 52655 Cov.: 0 AF XY: 0.567 AC XY: 102501 AN XY: 180720

Gnomad4 AFR exome AF: 0.594

Gnomad4 AMR exome AF: 0.698

Gnomad4 ASJ exome AF: 0.565

Gnomad4 EAS exome AF: 0.556

Gnomad4 SAS exome AF: 0.546

Gnomad4 FIN exome AF: 0.526

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.579 AC: 87950 AN: 151912 Hom.: 25707 Cov.: 30 AF XY: 0.576 AC XY: 42735 AN XY: 74220

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.595

Alfa AF: 0.572 Hom.: 7115

Bravo AF: 0.597

Asia WGS AF: 0.608 AC: 2117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.5
Dann	Benign	0.80

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: rs11899983; hg19: chr2-233415978;