chr1-21083738-C-A

Position:

• chr1-21083738-C-A

Variant summary

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

The NM_001391906.1(EIF4G3):​c.-196+5400G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,942 control chromosomes in the GnomAD database, including 12,690 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 0.40 (12690 hom., cov: 31)
• Consequence: EIF4G3 NM_001391906.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.919

Genes affected

EIF4G3 (HGNC:3298): (eukaryotic translation initiation factor 4 gamma 3) The protein encoded by this gene is thought to be part of the eIF4F protein complex, which is involved in mRNA cap recognition and transport of mRNAs to the ribosome. Interestingly, a microRNA (miR-520c-3p) has been found that negatively regulates synthesis of the encoded protein, and this leads to a global decrease in protein translation and cell proliferation. Therefore, this protein is a key component of the anti-tumor activity of miR-520c-3p. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4G3	NM_001391906.1	c.-196+5400G>T		intron_variant		ENST00000602326.6	NP_001378835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4G3	ENST00000602326.6	c.-196+5400G>T		intron_variant		1	NM_001391906.1	ENSP00000473510	A2

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61333 AN: 151824 Hom.: 12695 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.404 AC: 61365 AN: 151942 Hom.: 12690 Cov.: 31 AF XY: 0.400 AC XY: 29730 AN XY: 74240

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.400

Alfa AF: 0.427 Hom.: 2862

Bravo AF: 0.393

Asia WGS AF: 0.299 AC: 1041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.2
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4654899; hg19: chr1-21410231;