rs182428269

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_006164.5(NFE2L2):c.127C>T(p.Arg43Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000898 in 1,613,922 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R43Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000086 ( 1 hom. )

Consequence

NFE2L2
NM_006164.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 5.44

Publications

11 publications found

Variant links:

Genes affected

NFE2L2 (HGNC:7782): (NFE2 like bZIP transcription factor 2) This gene encodes a transcription factor which is a member of a small family of basic leucine zipper (bZIP) proteins. The encoded transcription factor regulates genes which contain antioxidant response elements (ARE) in their promoters; many of these genes encode proteins involved in response to injury and inflammation which includes the production of free radicals. Multiple transcript variants encoding different isoforms have been characterized for this gene. [provided by RefSeq, Sep 2015]

NFE2L2 Gene-Disease associations (from GenCC):

immunodeficiency, developmental delay, and hypohomocysteinemia
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P

NFE2L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09823206).

BP6

Variant 2-177234190-G-A is Benign according to our data. Variant chr2-177234190-G-A is described in ClinVar as [Benign]. Clinvar id is 134898.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L2	NM_006164.5 link	c.127C>T	p.Arg43Trp	missense_variant	Exon 2 of 5	ENST00000397062.8	NP_006155.2	Q16236-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFE2L2	ENST00000397062.8 link	c.127C>T	p.Arg43Trp	missense_variant	Exon 2 of 5	1	NM_006164.5	ENSP00000380252.3		Q16236-1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000104

AC:

AN:

249164

AF XY:

0.0000962

show subpopulations

Gnomad AFR exome

AF:

0.000646

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000862

AC:

126

AN:

1461812

Hom.:

Cov.:

AF XY:

0.0000756

AC XY:

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33474

American (AMR)

AF:

0.0000894

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000890

AC:

AN:

1111996

Other (OTH)

AF:

0.000116

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000125

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.000816

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000149

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

.;T;.;.;.;T;T;.;.;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

.;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.098

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.9

.;M;.;.;.;.;.;.;.;.

PhyloP100

5.4

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.5

N;D;N;.;N;D;.;D;D;.

REVEL

Benign

0.12

Sift

Uncertain

0.0010

D;D;D;.;D;D;.;D;D;.

Sift4G

Pathogenic

0.0010

D;D;D;D;.;.;D;.;D;.

Polyphen

0.98, 0.99

.;D;.;.;.;.;.;.;D;.

Vest4

0.19

MVP

0.23

MPC

0.40

ClinPred

0.14

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.24

gMVP

0.25

Mutation Taster

=67/33

polymorphism

(source)

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

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rs182428269

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over