dbSNP rs2292611: EIF2B5:n.36A>G (chr3-184135073-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000491144.5(EIF2B5):n.36A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 433,852 control chromosomes in the GnomAD database, including 16,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6793 hom., cov: 32)

Exomes 𝑓: 0.25 ( 9224 hom. )

Consequence

EIF2B5
ENST00000491144.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.787

Publications

8 publications found

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-DT (HGNC:55202): (EIF2B5 divergent transcript)

EIF2B5-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 3-184135073-A-G is Benign according to our data. Variant chr3-184135073-A-G is described in ClinVar as Benign. ClinVar VariationId is 344322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000491144.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
EIF2B5-DT	NR_183721.1	n.189T>C	non_coding_transcript_exon	Exon 1 of 2
EIF2B5-DT	NR_183718.1	n.67+122T>C	intron	N/A
EIF2B5-DT	NR_183719.1	n.67+122T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
EIF2B5	ENST00000491144.5	TSL:2	n.36A>G	non_coding_transcript_exon	Exon 1 of 15
EIF2B5-DT	ENST00000609288.2	TSL:6	n.307T>C	non_coding_transcript_exon	Exon 1 of 2
EIF2B5-DT	ENST00000716394.1		n.307T>C	non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43844

AN:

151834

Hom.:

6788

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.286

GnomAD4 exome

AF:

0.245

AC:

69067

AN:

281900

Hom.:

9224

Cov.:

AF XY:

0.245

AC XY:

36009

AN XY:

147184

show subpopulations

African (AFR)

AF:

0.390

AC:

3426

AN:

8782

American (AMR)

AF:

0.301

AC:

3299

AN:

10944

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

1796

AN:

8878

East Asian (EAS)

AF:

0.409

AC:

6964

AN:

17020

South Asian (SAS)

AF:

0.260

AC:

8772

AN:

33708

European-Finnish (FIN)

AF:

0.323

AC:

5213

AN:

16162

Middle Eastern (MID)

AF:

0.253

AC:

307

AN:

1214

European-Non Finnish (NFE)

AF:

0.209

AC:

35177

AN:

168614

Other (OTH)

AF:

0.248

AC:

4113

AN:

16578

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2415

4830

7244

9659

12074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

334

668

1002

1336

1670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.289

AC:

43889

AN:

151952

Hom.:

6793

Cov.:

AF XY:

0.294

AC XY:

21845

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.398

AC:

16475

AN:

41440

American (AMR)

AF:

0.288

AC:

4387

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

726

AN:

3472

East Asian (EAS)

AF:

0.402

AC:

2068

AN:

5142

South Asian (SAS)

AF:

0.267

AC:

1285

AN:

4816

European-Finnish (FIN)

AF:

0.337

AC:

3551

AN:

10552

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.215

AC:

14602

AN:

67964

Other (OTH)

AF:

0.284

AC:

599

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1533

3066

4599

6132

7665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.240

Hom.:

5217

Bravo

AF:

0.295

Asia WGS

AF:

0.333

AC:

1160

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Vanishing white matter disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.4

(source)

DANN

Benign

0.46

PhyloP100

-0.79

PromoterAI

-0.036

Neutral

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over