chr8-108279004-T-C

Position:

• chr8-108279004-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000677614.1(EIF3E):​c.-57-10582A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,166 control chromosomes in the GnomAD database, including 3,900 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 0.20 (3900 hom., cov: 32)
• Consequence: EIF3E ENST00000677614.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751

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]

EIF3E (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105375704	XR_928528.3	n.641-10582A>G		intron_variant
LOC105375704	XR_928529.3	n.237-10582A>G		intron_variant
LOC105375704	XR_928530.4	n.232-10582A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF3E	ENST00000677614.1	c.-57-10582A>G		intron_variant				ENSP00000504788.1
EIF3E	ENST00000678023.1	c.-57-10582A>G		intron_variant				ENSP00000502937.1
EIF3E	ENST00000678334.1	c.-57-10582A>G		intron_variant				ENSP00000503856.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31167 AN: 152046 Hom.: 3901 Cov.: 32

Gnomad AFR AF: 0.0696

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.205 AC: 31165 AN: 152166 Hom.: 3900 Cov.: 32 AF XY: 0.207 AC XY: 15377 AN XY: 74398

Gnomad4 AFR AF: 0.0695

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.202

Alfa AF: 0.231 Hom.: 9042

Bravo AF: 0.204

Asia WGS AF: 0.308 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.086
DANN	Benign	0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1975804; hg19: chr8-109291233;