dbSNP rs11211044: EIF2B3:c.1307-2077G>A (chr1-44853080-C-T) – 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.1307-2077G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,772 control chromosomes in the GnomAD database, including 14,924 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 0.43 ( 14924 hom., cov: 30)

Consequence

EIF2B3
NM_020365.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.51

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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2B3	NM_020365.5 link	c.1307-2077G>A		intron_variant	Intron 11 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.1307-2077G>A	intron_variant	Intron 11 of 11	1	NM_020365.5	ENSP00000353575.2	Q9NR50-1
EIF2B3	ENST00000620860.4 link	c.1203-2077G>A	intron_variant	Intron 10 of 10	1		ENSP00000483996.1	Q9NR50-3
EIF2B3	ENST00000439363.5 link	c.663-2077G>A	intron_variant	Intron 6 of 6	3		ENSP00000396985.1	H0Y580

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65224

AN:

151654

Hom.:

14894

Cov.:

show subpopulations

Gnomad AFR

AF:

0.587

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.467

Gnomad ASJ

AF:

0.320

Gnomad EAS

AF:

0.447

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.381

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

GnomAD4 genome

AF:

0.430

AC:

65314

AN:

151772

Hom.:

14924

Cov.:

AF XY:

0.429

AC XY:

31848

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.587

AC:

24258

AN:

41330

American (AMR)

AF:

0.468

AC:

7141

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.320

AC:

1106

AN:

3456

East Asian (EAS)

AF:

0.447

AC:

2300

AN:

5148

South Asian (SAS)

AF:

0.346

AC:

1665

AN:

4810

European-Finnish (FIN)

AF:

0.339

AC:

3565

AN:

10512

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.355

AC:

24149

AN:

67940

Other (OTH)

AF:

0.381

AC:

802

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1815

3630

5445

7260

9075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.378

Hom.:

8782

Bravo

AF:

0.448

Asia WGS

AF:

0.390

AC:

1354

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.82

(source)

DANN

Benign

0.74

PhyloP100

-1.5

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