rs138556551

Variant names:

• chr1-20817449-G-A
• rs138556551
• NM_001391906.1:c.4458C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-20817449-G-A
• chr1-20817449-G-C

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.4458C>T​(p.Leu1486Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000712 in 1,609,172 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00071 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (3 hom.)
• Consequence: EIF4G3 NM_001391906.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.14
• Publications: 0 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=-0.83).
• BP6: Variant 1-20817449-G-A is Benign according to our data. Variant chr1-20817449-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3250528.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.14 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 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.4458C>T	p.Leu1486Leu	synonymous	Exon 34 of 37	NP_001378835.1	A0A8J9G7U8
	EIF4G3	NM_001391907.1		c.4548C>T	p.Leu1516Leu	synonymous	Exon 34 of 37	NP_001378836.1
	EIF4G3	NM_001438678.1		c.4437C>T	p.Leu1479Leu	synonymous	Exon 33 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.4458C>T	p.Leu1486Leu	synonymous	Exon 34 of 37	ENSP00000473510.2	A0A8J9G7U8
	EIF4G3	ENST00000400422.6	TSL:1	c.4398C>T	p.Leu1466Leu	synonymous	Exon 32 of 35	ENSP00000383274.2	A0A0A0MSA7
	EIF4G3	ENST00000693470.1		c.5220C>T	p.Leu1740Leu	synonymous	Exon 30 of 33	ENSP00000509295.1	A0A8I5KV92

Frequencies

GnomAD3 genomes AF: 0.000707 AC: 107 AN: 151410 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000723

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000590

Gnomad OTH AF: 0.00242

GnomAD2 exomes AF: 0.000845 AC: 212 AN: 250884 AF XY: 0.000782

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000926

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000476

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000712 AC: 1038 AN: 1457646 Hom.: 3 Cov.: 30 AF XY: 0.000714 AC XY: 518 AN XY: 725116

African (AFR) AF: 0.0000898 AC: 3 AN: 33400

American (AMR) AF: 0.000940 AC: 42 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 264 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39556

South Asian (SAS) AF: 0.000152 AC: 13 AN: 85558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53058

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5754

European-Non Finnish (NFE) AF: 0.000556 AC: 617 AN: 1109494

Other (OTH) AF: 0.00151 AC: 91 AN: 60138

GnomAD4 genome AF: 0.000706 AC: 107 AN: 151526 Hom.: 1 Cov.: 32 AF XY: 0.000824 AC XY: 61 AN XY: 74048

African (AFR) AF: 0.000145 AC: 6 AN: 41458

American (AMR) AF: 0.000722 AC: 11 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000590 AC: 40 AN: 67846

Other (OTH) AF: 0.00239 AC: 5 AN: 2092

Alfa AF: 0.00121 Hom.: 1

Bravo AF: 0.000801

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	-0.83
CADD	Benign	0.047
DANN	Benign	0.58
PhyloP100		-4.1
Mutation Taster		=100/0	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: rs138556551; hg19: chr1-21143942; COSMIC: COSV51680059;