3-71746592-C-T

Variant summary

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

The ENST00000295612.7(EIF4E3):c.-291+6871G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,196 control chromosomes in the GnomAD database, including 2,753 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 0.19 (2753 hom., cov: 32)
• Consequence: EIF4E3 ENST00000295612.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4E3	NM_001134649.3	c.-291+7623G>A		intron_variant
EIF4E3	NM_001282886.2	c.-291+6871G>A		intron_variant
EIF4E3	NM_173359.5	c.-291+8052G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4E3	ENST00000295612.7	c.-291+6871G>A		intron_variant		1
EIF4E3	ENST00000421769.6	c.-291+8052G>A		intron_variant		1
EIF4E3	ENST00000448225.5	c.-291+7623G>A		intron_variant		5
EIF4E3	ENST00000496214.6	c.-291+7623G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28770 AN: 152078 Hom.: 2745 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.189 AC: 28796 AN: 152196 Hom.: 2753 Cov.: 32 AF XY: 0.190 AC XY: 14111 AN XY: 74398

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.180

Alfa AF: 0.164 Hom.: 2636

Bravo AF: 0.187

Asia WGS AF: 0.222 AC: 777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.9
Dann	Benign	0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6801173; hg19: chr3-71795743;