rs17008958

Positions:

• chr3-71706337-G-A
• chr3-71706337-G-C

Variant summary

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

The NM_001134651.2(EIF4E3):​c.249+4075C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,110 control chromosomes in the GnomAD database, including 1,732 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 0.14 (1732 hom., cov: 32)
• Consequence: EIF4E3 NM_001134651.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4E3	NM_001134651.2	c.249+4075C>T		intron_variant		ENST00000425534.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4E3	ENST00000425534.8	c.249+4075C>T		intron_variant		2	NM_001134651.2	P1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21976 AN: 151992 Hom.: 1727 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.145 AC: 22013 AN: 152110 Hom.: 1732 Cov.: 32 AF XY: 0.147 AC XY: 10902 AN XY: 74356

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.143

Alfa AF: 0.135 Hom.: 3132

Bravo AF: 0.140

Asia WGS AF: 0.264 AC: 921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.083
DANN	Benign	0.59

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: rs17008958; hg19: chr3-71755488;