3-71746592-C-T

Variant names:

• chr3-71746592-C-T
• rs6801173
• ENST00000647725.1:c.-959+7623G>A

Variant summary

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

The ENST00000647725.1(ENSG00000285708):​c.-959+7623G>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: ENSG00000285708 ENST00000647725.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421
• Publications: 7 publications found

Genes affected

ENSG00000285708 (HGNC:):

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EIF4E3	NM_001134649.3	c.-291+7623G>A		intron_variant	Intron 1 of 7		NP_001128121.1
EIF4E3	NM_001282886.2	c.-291+6871G>A		intron_variant	Intron 1 of 7		NP_001269815.1
EIF4E3	NM_173359.5	c.-291+8052G>A		intron_variant	Intron 1 of 7		NP_775495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285708	ENST00000647725.1	c.-959+7623G>A		intron_variant	Intron 1 of 25			ENSP00000497585.1

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

African (AFR) AF: 0.202 AC: 8402 AN: 41508

American (AMR) AF: 0.158 AC: 2416 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3470

East Asian (EAS) AF: 0.314 AC: 1623 AN: 5176

South Asian (SAS) AF: 0.134 AC: 647 AN: 4826

European-Finnish (FIN) AF: 0.219 AC: 2322 AN: 10584

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12141 AN: 68016

Other (OTH) AF: 0.180 AC: 380 AN: 2116

Alfa AF: 0.169 Hom.: 3843

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
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6801173; hg19: chr3-71795743;