1-21037690-T-C

Variant names:

• chr1-21037690-T-C
• rs959170
• NM_001391906.1:c.-67+13176A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001391906.1(EIF4G3):​c.-67+13176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 152,322 control chromosomes in the GnomAD database, including 134 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 0.029 (134 hom., cov: 32)
• Consequence: EIF4G3 NM_001391906.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.841
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

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.-67+13176A>G		intron	N/A	NP_001378835.1	A0A8J9G7U8
	EIF4G3	NM_001391907.1		c.-67+13176A>G		intron	N/A	NP_001378836.1
	EIF4G3	NM_001438678.1		c.-67+13176A>G		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.-67+13176A>G		intron	N/A	ENSP00000473510.2	A0A8J9G7U8
	EIF4G3	ENST00000400422.6	TSL:1	c.-67+13176A>G		intron	N/A	ENSP00000383274.2	A0A0A0MSA7
	EIF4G3	ENST00000356916.7	TSL:1	c.-67+13176A>G		intron	N/A	ENSP00000349386.3	O43432-2

Frequencies

GnomAD3 genomes AF: 0.0289 AC: 4401 AN: 152204 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0498

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0805

Gnomad FIN AF: 0.0421

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0216

Gnomad OTH AF: 0.0215

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

GnomAD4 genome AF: 0.0289 AC: 4402 AN: 152322 Hom.: 134 Cov.: 32 AF XY: 0.0312 AC XY: 2325 AN XY: 74478

African (AFR) AF: 0.0118 AC: 491 AN: 41582

American (AMR) AF: 0.0500 AC: 765 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3472

East Asian (EAS) AF: 0.141 AC: 728 AN: 5176

South Asian (SAS) AF: 0.0797 AC: 385 AN: 4828

European-Finnish (FIN) AF: 0.0421 AC: 447 AN: 10618

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0216 AC: 1469 AN: 68030

Other (OTH) AF: 0.0251 AC: 53 AN: 2114

Alfa AF: 0.0256 Hom.: 48

Bravo AF: 0.0285

Asia WGS AF: 0.112 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.4
DANN	Benign	0.68
PhyloP100		0.84
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: rs959170; hg19: chr1-21364183;