rs4654899

Variant names:

• chr1-21083738-C-A
• rs4654899
• NM_001391906.1:c.-196+5400G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EIF4G3	NM_001391906.1	c.-196+5400G>T		intron_variant	Intron 3 of 36	ENST00000602326.6	NP_001378835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4G3	ENST00000602326.6	c.-196+5400G>T		intron_variant	Intron 3 of 36	1	NM_001391906.1	ENSP00000473510.2
EIF4G3	ENST00000356916.7	c.-196+5400G>T		intron_variant	Intron 5 of 14	1		ENSP00000349386.3

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

African (AFR) AF: 0.378 AC: 15655 AN: 41406

American (AMR) AF: 0.383 AC: 5846 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1424 AN: 3472

East Asian (EAS) AF: 0.238 AC: 1231 AN: 5180

South Asian (SAS) AF: 0.366 AC: 1765 AN: 4822

European-Finnish (FIN) AF: 0.449 AC: 4722 AN: 10520

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29428 AN: 67964

Other (OTH) AF: 0.400 AC: 845 AN: 2110

Alfa AF: 0.421 Hom.: 19333

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
PhyloP100		0.92
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: rs4654899; hg19: chr1-21410231;