dbSNP rs12139143: EIF2B3:c.657-2617G>T (chr1-44884356-C-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.657-2617G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 151,936 control chromosomes in the GnomAD database, including 2,696 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 ( 2696 hom., cov: 31)

Consequence

EIF2B3
NM_020365.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.368

Publications

10 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=-0.87).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2B3	NM_020365.5 link	c.657-2617G>T		intron_variant	Intron 6 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.657-2617G>T	intron_variant	Intron 6 of 11	1	NM_020365.5	ENSP00000353575.2	Q9NR50-1
EIF2B3	ENST00000372183.7 link	c.657-2617G>T	intron_variant	Intron 6 of 9	1		ENSP00000361257.3	Q9NR50-2
EIF2B3	ENST00000620860.4 link	c.657-2617G>T	intron_variant	Intron 6 of 10	1		ENSP00000483996.1	Q9NR50-3
EIF2B3	ENST00000439363.5 link	c.117-2617G>T	intron_variant	Intron 2 of 6	3		ENSP00000396985.1	H0Y580

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27166

AN:

151818

Hom.:

2687

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.175

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

GnomAD4 genome

AF:

0.179

AC:

27193

AN:

151936

Hom.:

2696

Cov.:

AF XY:

0.181

AC XY:

13459

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.140

AC:

5800

AN:

41420

American (AMR)

AF:

0.280

AC:

4274

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

542

AN:

3470

East Asian (EAS)

AF:

0.277

AC:

1423

AN:

5140

South Asian (SAS)

AF:

0.183

AC:

882

AN:

4810

European-Finnish (FIN)

AF:

0.185

AC:

1954

AN:

10574

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.174

AC:

11821

AN:

67966

Other (OTH)

AF:

0.177

AC:

372

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1103

2206

3308

4411

5514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.171

Hom.:

3503

Bravo

AF:

0.184

Asia WGS

AF:

0.225

AC:

785

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.67

(source)

DANN

Benign

0.67

PhyloP100

-0.37

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