rs7620998

Variant names:

• chr3-71694655-A-G
• rs7620998
• NM_001134651.2:c.406-714T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134651.2(EIF4E3):​c.406-714T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,032 control chromosomes in the GnomAD database, including 7,266 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 0.31 (7266 hom., cov: 32)
• Consequence: EIF4E3 NM_001134651.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603
• Publications: 5 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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E3	NM_001134651.2	MANE Select	c.406-714T>C		intron	N/A	NP_001128123.1	Q8N5X7-1
	EIF4E3	NM_001134649.3		c.88-714T>C		intron	N/A	NP_001128121.1	Q8N5X7-2
	EIF4E3	NM_001134650.1		c.88-714T>C		intron	N/A	NP_001128122.1	Q8N5X7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E3	ENST00000425534.8	TSL:2 MANE Select	c.406-714T>C		intron	N/A	ENSP00000393324.2	Q8N5X7-1
	ENSG00000285708	ENST00000647725.1		c.-642-714T>C		intron	N/A	ENSP00000497585.1
	EIF4E3	ENST00000295612.7	TSL:1	c.88-714T>C		intron	N/A	ENSP00000295612.3	Q8N5X7-2

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46524 AN: 151914 Hom.: 7251 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.306 AC: 46569 AN: 152032 Hom.: 7266 Cov.: 32 AF XY: 0.313 AC XY: 23240 AN XY: 74306

African (AFR) AF: 0.287 AC: 11906 AN: 41474

American (AMR) AF: 0.277 AC: 4237 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 828 AN: 3472

East Asian (EAS) AF: 0.293 AC: 1516 AN: 5166

South Asian (SAS) AF: 0.354 AC: 1706 AN: 4822

European-Finnish (FIN) AF: 0.393 AC: 4146 AN: 10546

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21297 AN: 67956

Other (OTH) AF: 0.296 AC: 624 AN: 2108

Alfa AF: 0.305 Hom.: 9815

Bravo AF: 0.292

Asia WGS AF: 0.297 AC: 1035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.4
DANN	Benign	0.84
PhyloP100		-0.60
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: rs7620998; hg19: chr3-71743806;