rs11556200

Variant names:

Variant summary

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

The NM_020365.5(EIF2B3):c.243C>T(p.Asp81Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,613,288 control chromosomes in the GnomAD database, including 53,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6841 hom., cov: 32)

Exomes 𝑓: 0.25 ( 46589 hom. )

Consequence

EIF2B3
NM_020365.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.603

Variant links:

Genes affected

EIF2B3 (HGNC:3259): (eukaryotic translation initiation factor 2B subunit gamma) The protein encoded by this gene is one of the subunits of initiation factor eIF2B, which catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. It has also been found to function as a cofactor of hepatitis C virus internal ribosome entry site-mediated translation. Mutations in this gene have been associated with leukodystrophy with vanishing white matter. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

EIF2B3 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=-0.82).

BP6

Variant 1-44978366-G-A is Benign according to our data. Variant chr1-44978366-G-A is described in ClinVar as [Benign]. Clinvar id is 95947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.603 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2B3	NM_020365.5 link	c.243C>T	p.Asp81Asp	synonymous_variant	Exon 3 of 12	ENST00000360403.7	NP_065098.1	Q9NR50-1Q9HA31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF2B3	ENST00000360403.7 link	c.243C>T	p.Asp81Asp	synonymous_variant	Exon 3 of 12	1	NM_020365.5	ENSP00000353575.2		Q9NR50-1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43674

AN:

151808

Hom.:

6831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.387

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.288

GnomAD3 exomes

AF:

0.264

AC:

66428

AN:

251372

Hom.:

9609

AF XY:

0.253

AC XY:

34365

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.388

Gnomad AMR exome

AF:

0.403

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.260

Gnomad SAS exome

AF:

0.203

Gnomad FIN exome

AF:

0.219

Gnomad NFE exome

AF:

0.233

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.248

AC:

362943

AN:

1461362

Hom.:

46589

Cov.:

AF XY:

0.245

AC XY:

178271

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.393

Gnomad4 AMR exome

AF:

0.398

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.253

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.223

Gnomad4 NFE exome

AF:

0.242

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.288

AC:

43700

AN:

151926

Hom.:

6841

Cov.:

AF XY:

0.285

AC XY:

21126

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.386

Gnomad4 AMR

AF:

0.352

Gnomad4 ASJ

AF:

0.234

Gnomad4 EAS

AF:

0.267

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.210

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.285

Alfa

AF:

0.250

Hom.:

6686

Bravo

AF:

0.303

Asia WGS

AF:

0.242

AC:

843

AN:

3478

EpiCase

AF:

0.225

EpiControl

AF:

0.224

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Nov 06, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Nov 24, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Vanishing white matter disease

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.5

DANN

Benign

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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