Variant rs3738248 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_020365.5(EIF2B3):c.975+44A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,601,584 control chromosomes in the GnomAD database, including 23,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1839 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21263 hom. )

Consequence

EIF2B3
NM_020365.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.280

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 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=-0.77).

BP6

Variant 1-44879774-T-A is Benign according to our data. Variant chr1-44879774-T-A is described in ClinVar as [Benign]. Clinvar id is 261223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2B3	NM_020365.5 linkuse as main transcript	c.975+44A>T		intron_variant		ENST00000360403.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
EIF2B3	ENST00000360403.7 linkuse as main transcript	c.975+44A>T	intron_variant	1	NM_020365.5	P1	Q9NR50-1
EIF2B3	ENST00000372183.7 linkuse as main transcript	c.975+44A>T	intron_variant	1			Q9NR50-2
EIF2B3	ENST00000620860.4 linkuse as main transcript	c.975+44A>T	intron_variant	1			Q9NR50-3
EIF2B3	ENST00000439363.5 linkuse as main transcript	c.437+44A>T	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22840

AN:

152058

Hom.:

1830

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.143

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.140

GnomAD3 exomes

AF:

0.162

AC:

40562

AN:

250510

Hom.:

3401

AF XY:

0.162

AC XY:

22006

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.155

Gnomad ASJ exome

AF:

0.165

Gnomad EAS exome

AF:

0.165

Gnomad SAS exome

AF:

0.160

Gnomad FIN exome

AF:

0.145

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.170

AC:

247002

AN:

1449406

Hom.:

21263

Cov.:

AF XY:

0.170

AC XY:

122581

AN XY:

721714

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.167

Gnomad4 EAS exome

AF:

0.183

Gnomad4 SAS exome

AF:

0.162

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.175

Gnomad4 OTH exome

AF:

0.162

GnomAD4 genome

AF:

0.150

AC:

22883

AN:

152178

Hom.:

1839

Cov.:

AF XY:

0.149

AC XY:

11104

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.112

Gnomad4 AMR

AF:

0.149

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.160

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.143

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.163

Hom.:

361

Bravo

AF:

0.151

Asia WGS

AF:

0.135

AC:

470

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.4

DANN

Benign

0.68

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