3-71708266-G-A

Variant names:

• chr3-71708266-G-A
• rs1447899
• NM_001134651.2:c.249+2146C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ENSG00000285708 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134651.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E3	NM_001134651.2	MANE Select	c.249+2146C>T		intron	N/A	NP_001128123.1
	EIF4E3	NM_001134649.3		c.-70+2146C>T		intron	N/A	NP_001128121.1
	EIF4E3	NM_001134650.1		c.-70+2146C>T		intron	N/A	NP_001128122.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E3	ENST00000425534.8	TSL:2 MANE Select	c.249+2146C>T		intron	N/A	ENSP00000393324.2
	ENSG00000285708	ENST00000647725.1		c.-738+2146C>T		intron	N/A	ENSP00000497585.1
	EIF4E3	ENST00000295612.7	TSL:1	c.-70+2146C>T		intron	N/A	ENSP00000295612.3

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

African (AFR) AF: 0.462 AC: 19105 AN: 41392

American (AMR) AF: 0.235 AC: 3588 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2403 AN: 5172

South Asian (SAS) AF: 0.230 AC: 1106 AN: 4814

European-Finnish (FIN) AF: 0.328 AC: 3461 AN: 10538

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18760 AN: 67952

Other (OTH) AF: 0.310 AC: 655 AN: 2110

Alfa AF: 0.286 Hom.: 21000

Bravo AF: 0.330

Asia WGS AF: 0.377 AC: 1313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.011
DANN	Benign	0.63
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1447899; hg19: chr3-71757417;