rs1447899

chr3-71708266-G-Achr3-71708266-G-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+2146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,908 control chromosomes in the GnomAD database, including 8,908 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 0.33 (8908 hom., cov: 31)
• Consequence: EIF4E3 NM_001134651.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4E3	NM_001134651.2	c.249+2146C>T		intron_variant		ENST00000425534.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4E3	ENST00000425534.8	c.249+2146C>T		intron_variant		2	NM_001134651.2	P1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50034 AN: 151790 Hom.: 8890 Cov.: 31

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.330 AC: 50094 AN: 151908 Hom.: 8908 Cov.: 31 AF XY: 0.329 AC XY: 24387 AN XY: 74230

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.310

Alfa AF: 0.275 Hom.: 12293

Bravo AF: 0.330

Asia WGS AF: 0.377 AC: 1313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.011
Dann	Benign	0.63

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: rs1447899; hg19: chr3-71757417;