Variant chr1-44897320-T-C 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.656+35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,458,560 control chromosomes in the GnomAD database, including 270,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 37153 hom., cov: 33)

Exomes 𝑓: 0.59 ( 233700 hom. )

Consequence

EIF2B3
NM_020365.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.40

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 1-44897320-T-C is Benign according to our data. Variant chr1-44897320-T-C is described in ClinVar as [Benign]. Clinvar id is 261222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2B3	NM_020365.5 linkuse as main transcript	c.656+35A>G		intron_variant		ENST00000360403.7	NP_065098.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
EIF2B3	ENST00000360403.7 linkuse as main transcript	c.656+35A>G	intron_variant	1	NM_020365.5	ENSP00000353575	P1	Q9NR50-1
EIF2B3	ENST00000372183.7 linkuse as main transcript	c.656+35A>G	intron_variant	1		ENSP00000361257		Q9NR50-2
EIF2B3	ENST00000620860.4 linkuse as main transcript	c.656+35A>G	intron_variant	1		ENSP00000483996		Q9NR50-3
EIF2B3	ENST00000439363.5 linkuse as main transcript	c.118+35A>G	intron_variant	3		ENSP00000396985

Frequencies

GnomAD3 genomes

AF:

0.678

AC:

103142

AN:

152050

Hom.:

37076

Cov.:

show subpopulations

Gnomad AFR

AF:

0.904

Gnomad AMI

AF:

0.441

Gnomad AMR

AF:

0.709

Gnomad ASJ

AF:

0.556

Gnomad EAS

AF:

0.976

Gnomad SAS

AF:

0.661

Gnomad FIN

AF:

0.515

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.550

Gnomad OTH

AF:

0.639

GnomAD3 exomes

AF:

0.649

AC:

156822

AN:

241798

Hom.:

53519

AF XY:

0.633

AC XY:

82626

AN XY:

130474

show subpopulations

Gnomad AFR exome

AF:

0.908

Gnomad AMR exome

AF:

0.789

Gnomad ASJ exome

AF:

0.564

Gnomad EAS exome

AF:

0.974

Gnomad SAS exome

AF:

0.653

Gnomad FIN exome

AF:

0.525

Gnomad NFE exome

AF:

0.547

Gnomad OTH exome

AF:

0.591

GnomAD4 exome

AF:

0.588

AC:

768363

AN:

1306392

Hom.:

233700

Cov.:

AF XY:

0.587

AC XY:

385987

AN XY:

657710

show subpopulations

Gnomad4 AFR exome

AF:

0.915

Gnomad4 AMR exome

AF:

0.778

Gnomad4 ASJ exome

AF:

0.560

Gnomad4 EAS exome

AF:

0.983

Gnomad4 SAS exome

AF:

0.650

Gnomad4 FIN exome

AF:

0.536

Gnomad4 NFE exome

AF:

0.551

Gnomad4 OTH exome

AF:

0.610

GnomAD4 genome

AF:

0.679

AC:

103283

AN:

152168

Hom.:

37153

Cov.:

AF XY:

0.680

AC XY:

50548

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.904

Gnomad4 AMR

AF:

0.709

Gnomad4 ASJ

AF:

0.556

Gnomad4 EAS

AF:

0.975

Gnomad4 SAS

AF:

0.662

Gnomad4 FIN

AF:

0.515

Gnomad4 NFE

AF:

0.550

Gnomad4 OTH

AF:

0.644

Alfa

AF:

0.626

Hom.:

8558

Bravo

AF:

0.702

Asia WGS

AF:

0.852

AC:

2958

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

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

-0.93

CADD

Benign

1.2

DANN

Benign

0.21

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