rs12629971

Variant names:

• chr3-71734167-C-T
• rs12629971
• ENST00000647725.1:c.-958-5544G>A

Variant summary

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

The ENST00000647725.1(ENSG00000285708):​c.-958-5544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,144 control chromosomes in the GnomAD database, including 2,322 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 0.17 (2322 hom., cov: 33)
• Consequence: ENSG00000285708 ENST00000647725.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.944
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4E3	NM_001134649.3	c.-290-5544G>A		intron_variant	Intron 1 of 7		NP_001128121.1
EIF4E3	NM_001282886.2	c.-290-5544G>A		intron_variant	Intron 1 of 7		NP_001269815.1
EIF4E3	NM_173359.5	c.-290-5544G>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.-958-5544G>A		intron_variant	Intron 1 of 25			ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26278 AN: 152026 Hom.: 2316 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.173 AC: 26304 AN: 152144 Hom.: 2322 Cov.: 33 AF XY: 0.173 AC XY: 12897 AN XY: 74370

African (AFR) AF: 0.193 AC: 8005 AN: 41504

American (AMR) AF: 0.145 AC: 2223 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3472

East Asian (EAS) AF: 0.315 AC: 1632 AN: 5178

South Asian (SAS) AF: 0.124 AC: 598 AN: 4818

European-Finnish (FIN) AF: 0.199 AC: 2098 AN: 10568

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

European-Non Finnish (NFE) AF: 0.155 AC: 10553 AN: 67992

Other (OTH) AF: 0.166 AC: 350 AN: 2114

Alfa AF: 0.156 Hom.: 988

Bravo AF: 0.172

Asia WGS AF: 0.219 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.64
PhyloP100		-0.94
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: rs12629971; hg19: chr3-71783318;