dbSNP rs7298287: EIF2B1:c.370-20A>G (chr12-123627176-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001414.4(EIF2B1):c.370-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0909 in 1,603,222 control chromosomes in the GnomAD database, including 13,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 5082 hom., cov: 32)

Exomes 𝑓: 0.081 ( 8457 hom. )

Consequence

EIF2B1
NM_001414.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -4.54

Variant links:

Genes affected

EIF2B1 (HGNC:3257): (eukaryotic translation initiation factor 2B subunit alpha) 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, Oct 2009]

EIF2B1 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=-0.86).

BP6

Variant 12-123627176-T-C is Benign according to our data. Variant chr12-123627176-T-C is described in ClinVar as [Benign]. Clinvar id is 93731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2B1	NM_001414.4 link	c.370-20A>G		intron_variant	Intron 4 of 8	ENST00000424014.7	NP_001405.1	Q14232-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EIF2B1	ENST00000424014.7 link	c.370-20A>G	intron_variant	Intron 4 of 8	1	NM_001414.4	ENSP00000416250.2	Q14232-1
EIF2B1	ENST00000537073.1 link	c.370-20A>G	intron_variant	Intron 4 of 4	2		ENSP00000444183.1	Q14232-2
EIF2B1	ENST00000539951.5 link	c.331-20A>G	intron_variant	Intron 3 of 6	5		ENSP00000438060.1	F5H0D0
EIF2B1	ENST00000534960.5 link	c.415-2314A>G	intron_variant	Intron 4 of 5	5		ENSP00000443172.1	H0YGG4

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28208

AN:

151924

Hom.:

5036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.0698

Gnomad EAS

AF:

0.0931

Gnomad SAS

AF:

0.152

Gnomad FIN

AF:

0.0516

Gnomad MID

AF:

0.0892

Gnomad NFE

AF:

0.0641

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.108

AC:

27245

AN:

251366

Hom.:

2912

AF XY:

0.103

AC XY:

14026

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.488

Gnomad AMR exome

AF:

0.0806

Gnomad ASJ exome

AF:

0.0690

Gnomad EAS exome

AF:

0.0983

Gnomad SAS exome

AF:

0.159

Gnomad FIN exome

AF:

0.0548

Gnomad NFE exome

AF:

0.0657

Gnomad OTH exome

AF:

0.0831

GnomAD4 exome

AF:

0.0809

AC:

117442

AN:

1451180

Hom.:

8457

Cov.:

AF XY:

0.0822

AC XY:

59389

AN XY:

722584

show subpopulations

Gnomad4 AFR exome

AF:

0.486

Gnomad4 AMR exome

AF:

0.0875

Gnomad4 ASJ exome

AF:

0.0681

Gnomad4 EAS exome

AF:

0.0750

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.0532

Gnomad4 NFE exome

AF:

0.0632

Gnomad4 OTH exome

AF:

0.0999

GnomAD4 genome

AF:

0.186

AC:

28316

AN:

152042

Hom.:

5082

Cov.:

AF XY:

0.184

AC XY:

13654

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.473

Gnomad4 AMR

AF:

0.130

Gnomad4 ASJ

AF:

0.0698

Gnomad4 EAS

AF:

0.0923

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.0516

Gnomad4 NFE

AF:

0.0641

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.0893

Hom.:

1506

Bravo

AF:

0.202

Asia WGS

AF:

0.173

AC:

602

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 09, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0020

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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