chr3-184143083-G-A

Position:

chr3-184143083-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003907.3(EIF2B5):c.1686G>A(p.Gln562Gln) variant causes a synonymous change. The variant allele was found at a frequency of 0.00309 in 1,613,952 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 11 hom. )

Consequence

EIF2B5
NM_003907.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 5.69

Variant links:

Genes affected

EIF2B5 (HGNC:3261): (eukaryotic translation initiation factor 2B subunit epsilon) This gene encodes one of five subunits of eukaryotic translation initiation factor 2B (EIF2B), a GTP exchange factor for eukaryotic initiation factor 2 and an essential regulator for protein synthesis. Mutations in this gene and the genes encoding other EIF2B subunits have been associated with leukoencephalopathy with vanishing white matter. [provided by RefSeq, Nov 2009]

EIF2B5 links:

EIF2B5 (HGNC:):

EIF2B5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 3-184143083-G-A is Benign according to our data. Variant chr3-184143083-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 259195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00217 (330/152346) while in subpopulation AMR AF= 0.00438 (67/15304). AF 95% confidence interval is 0.00354. There are 0 homozygotes in gnomad4. There are 149 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2B5	NM_003907.3 linkuse as main transcript	c.1686G>A	p.Gln562Gln	synonymous_variant	12/16	ENST00000648915.2	NP_003898.2	Q13144
EIF2B5	XM_011513265.1 linkuse as main transcript	c.936G>A	p.Gln312Gln	synonymous_variant	8/12		XP_011511567.1
EIF2B5	XM_011513266.4 linkuse as main transcript	c.849G>A	p.Gln283Gln	synonymous_variant	7/11		XP_011511568.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2B5	ENST00000648915.2 linkuse as main transcript	c.1686G>A	p.Gln562Gln	synonymous_variant	12/16		NM_003907.3	ENSP00000497160.1		Q13144

Frequencies

GnomAD3 genomes

AF:

0.00217

AC:

330

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00438

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00307

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00215

AC:

539

AN:

250890

Hom.:

AF XY:

0.00207

AC XY:

281

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.000499

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000328

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.00326

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00319

AC:

4656

AN:

1461606

Hom.:

Cov.:

AF XY:

0.00304

AC XY:

2210

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.000575

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00288

Gnomad4 NFE exome

AF:

0.00376

Gnomad4 OTH exome

AF:

0.00220

GnomAD4 genome

AF:

0.00217

AC:

330

AN:

152346

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00307

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00235

Hom.:

Bravo

AF:

0.00245

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00278

EpiControl

AF:

0.00249

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	EIF2B5: BP4 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Vanishing white matter disease

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Natera, Inc.	Mar 08, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.1

DANN

Benign

0.76

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