chr1-20807343-T-C

Variant names:

• chr1-20807343-T-C
• rs146669269
• NM_001391906.1:c.4902A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001391906.1(EIF4G3):​c.4902A>G​(p.Ala1634Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00729 in 1,605,852 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (52 hom.)
• Consequence: EIF4G3 NM_001391906.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.74
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-20807343-T-C is Benign according to our data. Variant chr1-20807343-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2638442.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.74 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 gene

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.4902A>G	p.Ala1634Ala	synonymous	Exon 37 of 37	NP_001378835.1	A0A8J9G7U8
	EIF4G3	NM_001391907.1		c.4992A>G	p.Ala1664Ala	synonymous	Exon 37 of 37	NP_001378836.1
	EIF4G3	NM_001438678.1		c.4881A>G	p.Ala1627Ala	synonymous	Exon 36 of 36	NP_001425607.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4G3	ENST00000602326.6	TSL:1 MANE Select	c.4902A>G	p.Ala1634Ala	synonymous	Exon 37 of 37	ENSP00000473510.2	A0A8J9G7U8
	EIF4G3	ENST00000400422.6	TSL:1	c.4842A>G	p.Ala1614Ala	synonymous	Exon 35 of 35	ENSP00000383274.2	A0A0A0MSA7
	EIF4G3	ENST00000693470.1		c.5664A>G	p.Ala1888Ala	synonymous	Exon 33 of 33	ENSP00000509295.1	A0A8I5KV92

Frequencies

GnomAD3 genomes AF: 0.00572 AC: 871 AN: 152218 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.00537

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00825

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00604 AC: 1505 AN: 249166 AF XY: 0.00653

Gnomad AFR exome AF: 0.00321

Gnomad AMR exome AF: 0.00367

Gnomad ASJ exome AF: 0.00339

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00610

Gnomad NFE exome AF: 0.00763

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.00746 AC: 10837 AN: 1453516 Hom.: 52 Cov.: 30 AF XY: 0.00757 AC XY: 5463 AN XY: 722048

African (AFR) AF: 0.00261 AC: 87 AN: 33334

American (AMR) AF: 0.00409 AC: 181 AN: 44238

Ashkenazi Jewish (ASJ) AF: 0.00296 AC: 77 AN: 25988

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39424

South Asian (SAS) AF: 0.00782 AC: 667 AN: 85322

European-Finnish (FIN) AF: 0.00603 AC: 321 AN: 53268

Middle Eastern (MID) AF: 0.00976 AC: 56 AN: 5738

European-Non Finnish (NFE) AF: 0.00812 AC: 8984 AN: 1106132

Other (OTH) AF: 0.00771 AC: 463 AN: 60072

GnomAD4 genome AF: 0.00571 AC: 870 AN: 152336 Hom.: 4 Cov.: 32 AF XY: 0.00564 AC XY: 420 AN XY: 74494

African (AFR) AF: 0.00274 AC: 114 AN: 41576

American (AMR) AF: 0.00503 AC: 77 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00683 AC: 33 AN: 4832

European-Finnish (FIN) AF: 0.00537 AC: 57 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00825 AC: 561 AN: 68030

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.00685 Hom.: 3

Bravo AF: 0.00533

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.5
DANN	Benign	0.53
PhyloP100		-2.7
Mutation Taster		=93/7	polymorphism

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: rs146669269; hg19: chr1-21133836; COSMIC: COSV99943990;