dbSNP rs10183914: NFE2L2:n.804G>A (chr2-177232938-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000423513.6(NFE2L2):n.804G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 480,368 control chromosomes in the GnomAD database, including 24,213 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 7914 hom., cov: 32)

Exomes 𝑓: 0.30 ( 16299 hom. )

Consequence

NFE2L2
ENST00000423513.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0320

Publications

25 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L2	NM_006164.5 link	c.402+312G>A		intron_variant	Intron 3 of 4	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.402+312G>A		intron_variant	Intron 3 of 4	1	NM_006164.5	ENSP00000380252.3		Q16236-1

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

48024

AN:

151880

Hom.:

7912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.267

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.0662

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.340

GnomAD4 exome

AF:

0.296

AC:

97169

AN:

328370

Hom.:

16299

Cov.:

AF XY:

0.291

AC XY:

49566

AN XY:

170528

show subpopulations

African (AFR)

AF:

0.326

AC:

2678

AN:

8214

American (AMR)

AF:

0.226

AC:

2437

AN:

10772

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

3922

AN:

11000

East Asian (EAS)

AF:

0.0413

AC:

1028

AN:

24900

South Asian (SAS)

AF:

0.126

AC:

2792

AN:

22218

European-Finnish (FIN)

AF:

0.294

AC:

6656

AN:

22668

Middle Eastern (MID)

AF:

0.289

AC:

453

AN:

1570

European-Non Finnish (NFE)

AF:

0.343

AC:

70867

AN:

206804

Other (OTH)

AF:

0.313

AC:

6336

AN:

20224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3021

6042

9062

12083

15104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

290

580

870

1160

1450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.316

AC:

48049

AN:

151998

Hom.:

7914

Cov.:

AF XY:

0.307

AC XY:

22808

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.331

AC:

13714

AN:

41448

American (AMR)

AF:

0.267

AC:

4077

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

1225

AN:

3470

East Asian (EAS)

AF:

0.0660

AC:

341

AN:

5168

South Asian (SAS)

AF:

0.128

AC:

618

AN:

4830

European-Finnish (FIN)

AF:

0.281

AC:

2963

AN:

10554

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.355

AC:

24126

AN:

67940

Other (OTH)

AF:

0.338

AC:

711

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1700

3400

5100

6800

8500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.321

Hom.:

1611

Bravo

AF:

0.320

Asia WGS

AF:

0.113

AC:

395

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.9

(source)

DANN

Benign

0.56

PhyloP100

-0.032

PromoterAI

0.0066

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over