Variant 2-177234189-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006164.5(NFE2L2):c.128G>A(p.Arg43Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000776 in 1,614,060 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R43W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0041 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00043 ( 2 hom. )

Consequence

NFE2L2
NM_006164.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 1.52

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043025613).

BP6

Variant 2-177234189-C-T is Benign according to our data. Variant chr2-177234189-C-T is described in ClinVar as [Benign]. Clinvar id is 134900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 620 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFE2L2	NM_006164.5 linkuse as main transcript	c.128G>A	p.Arg43Gln	missense_variant	2/5	ENST00000397062.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFE2L2	ENST00000397062.8 linkuse as main transcript	c.128G>A	p.Arg43Gln	missense_variant	2/5	1	NM_006164.5	A1	Q16236-1

Frequencies

GnomAD3 genomes

AF:

0.00407

AC:

619

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00117

AC:

291

AN:

249190

Hom.:

AF XY:

0.000895

AC XY:

121

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.0160

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000433

AC:

633

AN:

1461806

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

264

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0147

Gnomad4 AMR exome

AF:

0.000917

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.00407

AC:

620

AN:

152254

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

276

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0142

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.000621

Hom.:

Bravo

AF:

0.00494

ESP6500AA

AF:

0.0139

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00126

AC:

152

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.054

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

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.86

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

MetaRNN

Benign

0.0043

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

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.18

.;N;.;.;.;.;.;.;.;.

MutationTaster

Benign

0.98

N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

2.1

N;N;N;.;N;N;.;N;N;.

REVEL

Benign

0.061

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.0, 0.0050

.;B;.;.;.;.;.;.;B;.

Vest4

0.042

MVP

0.22

MPC

0.17

ClinPred

0.011

GERP RS

-0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.027

gMVP

0.053

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