Variant 14-75003066-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014239.4(EIF2B2):c.76G>C(p.Gly26Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000939 in 1,614,088 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00085 ( 10 hom. )

Consequence

EIF2B2
NM_014239.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.69

Variant links:

Genes affected

EIF2B2 (HGNC:3258): (eukaryotic translation initiation factor 2B subunit beta) This gene encodes the beta subunit of eukaryotic initiation factor-2B (EIF2B). EIF2B is involved in protein synthesis and exchanges GDP and GTP for its activation and deactivation. [provided by RefSeq, Aug 2011]

EIF2B2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00929755).

BP6

Variant 14-75003066-G-C is Benign according to our data. Variant chr14-75003066-G-C is described in ClinVar as [Benign]. Clinvar id is 753033.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2B2	NM_014239.4 linkuse as main transcript	c.76G>C	p.Gly26Arg	missense_variant	1/8	ENST00000266126.10	NP_055054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2B2	ENST00000266126.10 linkuse as main transcript	c.76G>C	p.Gly26Arg	missense_variant	1/8	1	NM_014239.4	ENSP00000266126	P1

Frequencies

GnomAD3 genomes

AF:

0.00184

AC:

280

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0232

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00218

AC:

547

AN:

250954

Hom.:

AF XY:

0.00208

AC XY:

283

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0230

Gnomad NFE exome

AF:

0.000335

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000846

AC:

1236

AN:

1461796

Hom.:

Cov.:

AF XY:

0.000822

AC XY:

598

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0210

Gnomad4 NFE exome

AF:

0.0000638

Gnomad4 OTH exome

AF:

0.000778

GnomAD4 genome

AF:

0.00184

AC:

280

AN:

152292

Hom.:

Cov.:

AF XY:

0.00285

AC XY:

212

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0232

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000670

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00170

AC:

207

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.099

Eigen

Benign

0.025

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0093

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.27

REVEL

Uncertain

0.52

Sift

Benign

0.16

Sift4G

Benign

0.57

Polyphen

0.053

Vest4

0.69

MVP

1.0

MPC

0.53

ClinPred

0.088

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.39

gMVP

0.60

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