1-20893882-T-G

Position:

• chr1-20893882-T-G

Variant summary

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

The NM_001391906.1(EIF4G3):​c.2134-246A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 146,314 control chromosomes in the GnomAD database, including 25,706 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 0.59 (25706 hom., cov: 22)
• Consequence: EIF4G3 NM_001391906.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4G3	NM_001391906.1	c.2134-246A>C		intron_variant		ENST00000602326.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4G3	ENST00000602326.6	c.2134-246A>C		intron_variant		1	NM_001391906.1	A2

Frequencies

GnomAD3 genomes AF: 0.589 AC: 86074 AN: 146196 Hom.: 25688 Cov.: 22

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.589 AC: 86149 AN: 146314 Hom.: 25706 Cov.: 22 AF XY: 0.593 AC XY: 42049 AN XY: 70890

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.602

Alfa AF: 0.567 Hom.: 3042

Bravo AF: 0.597

Asia WGS AF: 0.736 AC: 2563 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	0.64
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs2275468; hg19: chr1-21220375; COSMIC: COSV51695904;