1-21037690-T-C

Position:

• chr1-21037690-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4G3	NM_001391906.1	c.-67+13176A>G		intron_variant		ENST00000602326.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4G3	ENST00000602326.6	c.-67+13176A>G		intron_variant		1	NM_001391906.1	A2

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

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0500

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.0797

Gnomad4 FIN AF: 0.0421

Gnomad4 NFE AF: 0.0216

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0260 Hom.: 47

Bravo AF: 0.0285

Asia WGS AF: 0.112 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.4
DANN	Benign	0.68

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: rs959170; hg19: chr1-21364183;