8-108215779-A-G

Variant names:

• chr8-108215779-A-G
• rs611744
• NM_001568.3:c.951+633T>C

Variant summary

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

The NM_001568.3(EIF3E):​c.951+633T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,010 control chromosomes in the GnomAD database, including 21,294 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 0.52 (21294 hom., cov: 32)
• Consequence: EIF3E NM_001568.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• Publications: 26 publications found

Genes affected

EIF3E (HGNC:3277): (eukaryotic translation initiation factor 3 subunit E) Enables protein N-terminus binding activity. Contributes to translation initiation factor activity. Involved in positive regulation of mRNA binding activity; regulation of gene expression; and translational initiation. Located in cytosol and nucleus. Part of eukaryotic translation initiation factor 3 complex. Colocalizes with PML body. [provided by Alliance of Genome Resources, Apr 2022]

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 (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3E	NM_001568.3	c.951+633T>C		intron_variant	Intron 9 of 12	ENST00000220849.10	NP_001559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3E	ENST00000220849.10	c.951+633T>C		intron_variant	Intron 9 of 12	1	NM_001568.3	ENSP00000220849.5

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79587 AN: 151892 Hom.: 21245 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.524 AC: 79698 AN: 152010 Hom.: 21294 Cov.: 32 AF XY: 0.526 AC XY: 39095 AN XY: 74302

African (AFR) AF: 0.657 AC: 27242 AN: 41436

American (AMR) AF: 0.467 AC: 7132 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1672 AN: 3470

East Asian (EAS) AF: 0.498 AC: 2575 AN: 5166

South Asian (SAS) AF: 0.528 AC: 2547 AN: 4822

European-Finnish (FIN) AF: 0.501 AC: 5288 AN: 10550

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31653 AN: 67968

Other (OTH) AF: 0.512 AC: 1082 AN: 2112

Alfa AF: 0.477 Hom.: 68688

Bravo AF: 0.526

Asia WGS AF: 0.558 AC: 1943 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	3.3
DANN	Benign	0.39
PhyloP100		0.18
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: rs611744; hg19: chr8-109228008;