1-21003621-G-C

Variant names:

• chr1-21003621-G-C
• rs10493005
• NM_001391906.1:c.-66-813C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001391906.1(EIF4G3):​c.-66-813C>G variant causes a intron change. The variant allele was found at a frequency of 0.0205 in 326,596 control chromosomes in the GnomAD database, including 105 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 0.020 (60 hom., cov: 32)
  • Exomes 𝑓: 0.020 (45 hom.)
• Consequence: EIF4G3 NM_001391906.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.78

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]

RPS15AP6 (HGNC:35657): (ribosomal protein S15a pseudogene 6)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0205 (3117/152210) while in subpopulation NFE AF= 0.0265 (1805/68010). AF 95% confidence interval is 0.0255. There are 60 homozygotes in gnomad4. There are 1604 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 60 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4G3	NM_001391906.1	c.-66-813C>G		intron_variant	Intron 4 of 36	ENST00000602326.6	NP_001378835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4G3	ENST00000602326.6	c.-66-813C>G		intron_variant	Intron 4 of 36	1	NM_001391906.1	ENSP00000473510.2
EIF4G3	ENST00000356916.7	c.-66-813C>G		intron_variant	Intron 6 of 14	1		ENSP00000349386.3

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 3121 AN: 152090 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.00490

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0211

GnomAD4 exome AF: 0.0205 AC: 3569 AN: 174386 Hom.: 45 Cov.: 0 AF XY: 0.0194 AC XY: 1989 AN XY: 102662

Gnomad4 AFR exome AF: 0.00569

Gnomad4 AMR exome AF: 0.00569

Gnomad4 ASJ exome AF: 0.0170

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00521

Gnomad4 FIN exome AF: 0.0454

Gnomad4 NFE exome AF: 0.0258

Gnomad4 OTH exome AF: 0.0266

GnomAD4 genome AF: 0.0205 AC: 3117 AN: 152210 Hom.: 60 Cov.: 32 AF XY: 0.0216 AC XY: 1604 AN XY: 74402

Gnomad4 AFR AF: 0.00489

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00498

Gnomad4 FIN AF: 0.0637

Gnomad4 NFE AF: 0.0265

Gnomad4 OTH AF: 0.0209

Alfa AF: 0.0133 Hom.: 5

Bravo AF: 0.0168

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.77

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: rs10493005; hg19: chr1-21330114;