rs4677039

Positions:

• chr3-71707614-C-T

Variant summary

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

The NM_001134651.2(EIF4E3):​c.249+2798G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,828 control chromosomes in the GnomAD database, including 6,093 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 0.26 (6093 hom., cov: 31)
• Consequence: EIF4E3 NM_001134651.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

EIF4E3 (HGNC:31837): (eukaryotic translation initiation factor 4E family member 3) EIF4E3 belongs to the EIF4E family of translational initiation factors that interact with the 5-prime cap structure of mRNA and recruit mRNA to the ribosome (Joshi et al., 2004 [PubMed 15153109]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4E3	NM_001134651.2	c.249+2798G>A		intron_variant		ENST00000425534.8	NP_001128123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4E3	ENST00000425534.8	c.249+2798G>A		intron_variant		2	NM_001134651.2	ENSP00000393324	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39617 AN: 151710 Hom.: 6092 Cov.: 31

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.261 AC: 39618 AN: 151828 Hom.: 6093 Cov.: 31 AF XY: 0.264 AC XY: 19607 AN XY: 74196

Gnomad4 AFR AF: 0.0969

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.281

Alfa AF: 0.322 Hom.: 9072

Bravo AF: 0.247

Asia WGS AF: 0.247 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.96

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: rs4677039; hg19: chr3-71756765;