Variant rs7571971 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 ENST00000303236.9(EIF2AK3):c.439-170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 723,880 control chromosomes in the GnomAD database, including 191,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45999 hom., cov: 31)

Exomes 𝑓: 0.71 ( 145015 hom. )

Consequence

EIF2AK3
ENST00000303236.9 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.64

Variant links:

Genes affected

EIF2AK3 (HGNC:3255): (eukaryotic translation initiation factor 2 alpha kinase 3) The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protein is thought to modulate mitochondrial function. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in this gene are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Sep 2015]

EIF2AK3 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=-0.92).

BP6

Variant 2-88595833-T-C is Benign according to our data. Variant chr2-88595833-T-C is described in ClinVar as [Benign]. Clinvar id is 1174990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-88595833-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
EIF2AK3	NM_004836.7 linkuse as main transcript	c.439-170A>G	intron_variant	ENST00000303236.9	NP_004827.4
EIF2AK3	NM_001313915.2 linkuse as main transcript	c.-15-170A>G	intron_variant		NP_001300844.1
EIF2AK3	XM_047446428.1 linkuse as main transcript	c.148-170A>G	intron_variant		XP_047302384.1
EIF2AK3	XM_047446430.1 linkuse as main transcript	c.439-170A>G	intron_variant		XP_047302386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2AK3	ENST00000303236.9 linkuse as main transcript	c.439-170A>G		intron_variant		1	NM_004836.7	ENSP00000307235	P1

Frequencies

GnomAD3 genomes

AF:

0.768

AC:

116673

AN:

151920

Hom.:

45947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.944

Gnomad AMI

AF:

0.671

Gnomad AMR

AF:

0.685

Gnomad ASJ

AF:

0.784

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.752

Gnomad NFE

AF:

0.728

Gnomad OTH

AF:

0.723

GnomAD3 exomes

AF:

0.697

AC:

94622

AN:

135836

Hom.:

33574

AF XY:

0.689

AC XY:

50694

AN XY:

73524

show subpopulations

Gnomad AFR exome

AF:

0.951

Gnomad AMR exome

AF:

0.687

Gnomad ASJ exome

AF:

0.781

Gnomad EAS exome

AF:

0.508

Gnomad SAS exome

AF:

0.626

Gnomad FIN exome

AF:

0.660

Gnomad NFE exome

AF:

0.728

Gnomad OTH exome

AF:

0.691

GnomAD4 exome

AF:

0.708

AC:

404680

AN:

571842

Hom.:

145015

Cov.:

AF XY:

0.704

AC XY:

216948

AN XY:

308378

show subpopulations

Gnomad4 AFR exome

AF:

0.942

Gnomad4 AMR exome

AF:

0.685

Gnomad4 ASJ exome

AF:

0.770

Gnomad4 EAS exome

AF:

0.553

Gnomad4 SAS exome

AF:

0.623

Gnomad4 FIN exome

AF:

0.660

Gnomad4 NFE exome

AF:

0.728

Gnomad4 OTH exome

AF:

0.723

GnomAD4 genome

AF:

0.768

AC:

116780

AN:

152038

Hom.:

45999

Cov.:

AF XY:

0.759

AC XY:

56400

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.945

Gnomad4 AMR

AF:

0.685

Gnomad4 ASJ

AF:

0.784

Gnomad4 EAS

AF:

0.527

Gnomad4 SAS

AF:

0.615

Gnomad4 FIN

AF:

0.652

Gnomad4 NFE

AF:

0.728

Gnomad4 OTH

AF:

0.721

Alfa

AF:

0.726

Hom.:

40880

Bravo

AF:

0.780

Asia WGS

AF:

0.631

AC:

2196

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.7

DANN

Benign

0.48

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