dbSNP rs12733586: EIF2B3:c.1203-3751C>T (chr1-44861558-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020365.5(EIF2B3):c.1203-3751C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,074 control chromosomes in the GnomAD database, including 2,738 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2738 hom., cov: 32)

Consequence

EIF2B3
NM_020365.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.91

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

leukoencephalopathy with vanishing white matter
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
leukoencephalopathy with vanishing white matter 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
ovarioleukodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

EIF2B3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2B3	NM_020365.5 link	c.1203-3751C>T		intron_variant	Intron 10 of 11	ENST00000360403.7	NP_065098.1	Q9NR50-1Q9HA31

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EIF2B3	ENST00000360403.7 link	c.1203-3751C>T	intron_variant	Intron 10 of 11	1	NM_020365.5	ENSP00000353575.2	Q9NR50-1
EIF2B3	ENST00000620860.4 link	c.1203-10555C>T	intron_variant	Intron 10 of 10	1		ENSP00000483996.1	Q9NR50-3
EIF2B3	ENST00000439363.5 link	c.663-10555C>T	intron_variant	Intron 6 of 6	3		ENSP00000396985.1	H0Y580

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27456

AN:

151956

Hom.:

2728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.187

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.177

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.181

AC:

27485

AN:

152074

Hom.:

2738

Cov.:

AF XY:

0.183

AC XY:

13601

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.146

AC:

6038

AN:

41490

American (AMR)

AF:

0.281

AC:

4292

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

541

AN:

3470

East Asian (EAS)

AF:

0.276

AC:

1431

AN:

5178

South Asian (SAS)

AF:

0.187

AC:

901

AN:

4816

European-Finnish (FIN)

AF:

0.184

AC:

1945

AN:

10570

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.174

AC:

11836

AN:

67970

Other (OTH)

AF:

0.178

AC:

376

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1140

2281

3421

4562

5702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.186

Hom.:

331

Bravo

AF:

0.186

Asia WGS

AF:

0.226

AC:

788

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.56

PhyloP100

2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over