Variant 12-123626387-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001414.4(EIF2B1):c.551+38C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 1,612,310 control chromosomes in the GnomAD database, including 3,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 574 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2515 hom. )

Consequence

EIF2B1
NM_001414.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0980

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=-0.85).

BP6

Variant 12-123626387-G-T is Benign according to our data. Variant chr12-123626387-G-T is described in ClinVar as [Benign]. Clinvar id is 258092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2B1	NM_001414.4 linkuse as main transcript	c.551+38C>A		intron_variant		ENST00000424014.7	NP_001405.1	Q14232-1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EIF2B1	ENST00000424014.7 linkuse as main transcript	c.551+38C>A	intron_variant		1	NM_001414.4	ENSP00000416250.2	Q14232-1
EIF2B1	ENST00000537073.1 linkuse as main transcript	c.*470C>A	3_prime_UTR_variant	5/5	2		ENSP00000444183.1	Q14232-2
EIF2B1	ENST00000539951.5 linkuse as main transcript	c.512+38C>A	intron_variant		5		ENSP00000438060.1	F5H0D0
EIF2B1	ENST00000534960.5 linkuse as main transcript	c.415-1525C>A	intron_variant		5		ENSP00000443172.1	H0YGG4

Frequencies

GnomAD3 genomes

AF:

0.0728

AC:

11073

AN:

152132

Hom.:

565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0325

Gnomad ASJ

AF:

0.0461

Gnomad EAS

AF:

0.0877

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0449

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0462

Gnomad OTH

AF:

0.0655

GnomAD3 exomes

AF:

0.0618

AC:

15515

AN:

251116

Hom.:

691

AF XY:

0.0628

AC XY:

8520

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.137

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.0475

Gnomad EAS exome

AF:

0.0918

Gnomad SAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.0466

Gnomad NFE exome

AF:

0.0486

Gnomad OTH exome

AF:

0.0495

GnomAD4 exome

AF:

0.0514

AC:

75089

AN:

1460060

Hom.:

2515

Cov.:

AF XY:

0.0533

AC XY:

38731

AN XY:

726454

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.0215

Gnomad4 ASJ exome

AF:

0.0452

Gnomad4 EAS exome

AF:

0.0713

Gnomad4 SAS exome

AF:

0.116

Gnomad4 FIN exome

AF:

0.0444

Gnomad4 NFE exome

AF:

0.0446

Gnomad4 OTH exome

AF:

0.0567

GnomAD4 genome

AF:

0.0730

AC:

11107

AN:

152250

Hom.:

574

Cov.:

AF XY:

0.0724

AC XY:

5390

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.135

Gnomad4 AMR

AF:

0.0324

Gnomad4 ASJ

AF:

0.0461

Gnomad4 EAS

AF:

0.0869

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.0449

Gnomad4 NFE

AF:

0.0462

Gnomad4 OTH

AF:

0.0738

Alfa

AF:

0.0622

Hom.:

Bravo

AF:

0.0725

Asia WGS

AF:

0.128

AC:

443

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.7

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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