1-20893882-T-G

Variant names:

• chr1-20893882-T-G
• rs2275468
• NM_001391906.1:c.2134-246A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.92).
• 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 rank	MANE	Protein	UniProt
EIF4G3	NM_001391906.1	c.2134-246A>C		intron_variant	Intron 17 of 36	ENST00000602326.6	NP_001378835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4G3	ENST00000602326.6	c.2134-246A>C		intron_variant	Intron 17 of 36	1	NM_001391906.1	ENSP00000473510.2

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

African (AFR) AF: 0.549 AC: 21532 AN: 39242

American (AMR) AF: 0.616 AC: 8707 AN: 14130

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2093 AN: 3442

East Asian (EAS) AF: 0.831 AC: 4163 AN: 5010

South Asian (SAS) AF: 0.636 AC: 2832 AN: 4454

European-Finnish (FIN) AF: 0.569 AC: 5551 AN: 9752

Middle Eastern (MID) AF: 0.654 AC: 191 AN: 292

European-Non Finnish (NFE) AF: 0.586 AC: 39328 AN: 67108

Other (OTH) AF: 0.602 AC: 1191 AN: 1978

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
PhyloP100		-0.79
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: rs2275468; hg19: chr1-21220375; COSMIC: COSV51695904;