rs2275468

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-20893882-T-A
• chr1-20893882-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001391906.1(EIF4G3):​c.2134-246A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001391906.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4G3	NM_001391906.1	MANE Select	c.2134-246A>T		intron	N/A	NP_001378835.1	A0A8J9G7U8
	EIF4G3	NM_001391907.1		c.2113-246A>T		intron	N/A	NP_001378836.1
	EIF4G3	NM_001438678.1		c.2113-246A>T		intron	N/A	NP_001425607.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4G3	ENST00000602326.6	TSL:1 MANE Select	c.2134-246A>T		intron	N/A	ENSP00000473510.2	A0A8J9G7U8
	EIF4G3	ENST00000400422.6	TSL:1	c.1963-246A>T		intron	N/A	ENSP00000383274.2	A0A0A0MSA7
	EIF4G3	ENST00000693470.1		c.2896-246A>T		intron	N/A	ENSP00000509295.1	A0A8I5KV92

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.61
DANN	Benign	0.44
PhyloP100		-0.79

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;