20-63494946-C-T

Position:

chr20-63494946-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001958.5(EEF1A2):c.480G>A(p.Pro160Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,612,748 control chromosomes in the GnomAD database, including 17,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1555 hom., cov: 34)

Exomes 𝑓: 0.13 ( 15458 hom. )

Consequence

EEF1A2
NM_001958.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.78

Variant links:

Genes affected

EEF1A2 (HGNC:3192): (eukaryotic translation elongation factor 1 alpha 2) This gene encodes an isoform of the alpha subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This isoform (alpha 2) is expressed in brain, heart and skeletal muscle, and the other isoform (alpha 1) is expressed in brain, placenta, lung, liver, kidney, and pancreas. This gene may be critical in the development of ovarian cancer. [provided by RefSeq, Mar 2014]

EEF1A2 links:

EEF1A2 (HGNC:):

EEF1A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 20-63494946-C-T is Benign according to our data. Variant chr20-63494946-C-T is described in ClinVar as [Benign]. Clinvar id is 380779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63494946-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.78 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEF1A2	NM_001958.5 linkuse as main transcript	c.480G>A	p.Pro160Pro	synonymous_variant	4/8	ENST00000217182.6	NP_001949.1	Q05639

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EEF1A2	ENST00000217182.6 linkuse as main transcript	c.480G>A	p.Pro160Pro	synonymous_variant	4/8	1	NM_001958.5	ENSP00000217182.3		Q05639

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17245

AN:

152172

Hom.:

1554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0256

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0895

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.0695

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.116

GnomAD3 exomes

AF:

0.139

AC:

34691

AN:

250166

Hom.:

3571

AF XY:

0.136

AC XY:

18400

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.0226

Gnomad AMR exome

AF:

0.0810

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.425

Gnomad SAS exome

AF:

0.0587

Gnomad FIN exome

AF:

0.224

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.131

AC:

191988

AN:

1460458

Hom.:

15458

Cov.:

AF XY:

0.129

AC XY:

93916

AN XY:

726520

show subpopulations

Gnomad4 AFR exome

AF:

0.0201

Gnomad4 AMR exome

AF:

0.0807

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.436

Gnomad4 SAS exome

AF:

0.0585

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.134

GnomAD4 genome

AF:

0.113

AC:

17242

AN:

152290

Hom.:

1555

Cov.:

AF XY:

0.119

AC XY:

8843

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0256

Gnomad4 AMR

AF:

0.0896

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.442

Gnomad4 SAS

AF:

0.0686

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.124

Hom.:

1963

Bravo

AF:

0.101

Asia WGS

AF:

0.206

AC:

714

AN:

3478

EpiCase

AF:

0.125

EpiControl

AF:

0.128

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 07, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

Developmental and epileptic encephalopathy, 33

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 31, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.41

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over