dbSNP rs6706649: NFE2L2:c.184-31072G>A (chr2-177265343-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 ENST00000699346.1(NFE2L2):c.184-31072G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 203,304 control chromosomes in the GnomAD database, including 1,065 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 0.088 ( 744 hom., cov: 34)

Exomes 𝑓: 0.10 ( 321 hom. )

Consequence

NFE2L2
ENST00000699346.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.707

Publications

51 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:

ENSG00000222043 (HGNC:):

ENSG00000222043 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=-0.63).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
NFE2L2	ENST00000699346.1 link	c.184-31072G>A	intron_variant	Intron 7 of 10		ENSP00000514321.1	A0A8V8TNM0
NFE2L2	ENST00000586532.6 link	c.43-31072G>A	intron_variant	Intron 3 of 6	5	ENSP00000464920.2	K7EIW5
NFE2L2	ENST00000699265.1 link	c.43-31072G>A	intron_variant	Intron 5 of 8		ENSP00000514246.1	K7EIW5

Frequencies

GnomAD3 genomes

AF:

0.0877

AC:

13345

AN:

152174

Hom.:

744

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0237

Gnomad AMI

AF:

0.0516

Gnomad AMR

AF:

0.0793

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.0605

Gnomad SAS

AF:

0.0981

Gnomad FIN

AF:

0.0978

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.0999

GnomAD4 exome

AF:

0.104

AC:

5308

AN:

51012

Hom.:

321

Cov.:

AF XY:

0.107

AC XY:

2551

AN XY:

23904

show subpopulations

African (AFR)

AF:

0.0185

AC:

AN:

2110

American (AMR)

AF:

0.0704

AC:

AN:

1378

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

560

AN:

3144

East Asian (EAS)

AF:

0.0478

AC:

397

AN:

8310

South Asian (SAS)

AF:

0.0750

AC:

AN:

480

European-Finnish (FIN)

AF:

0.107

AC:

AN:

140

Middle Eastern (MID)

AF:

0.105

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.119

AC:

3687

AN:

31002

Other (OTH)

AF:

0.107

AC:

445

AN:

4144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

215

430

646

861

1076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0876

AC:

13347

AN:

152292

Hom.:

744

Cov.:

AF XY:

0.0863

AC XY:

6422

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0237

AC:

986

AN:

41582

American (AMR)

AF:

0.0793

AC:

1214

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

664

AN:

3470

East Asian (EAS)

AF:

0.0604

AC:

312

AN:

5162

South Asian (SAS)

AF:

0.0983

AC:

475

AN:

4830

European-Finnish (FIN)

AF:

0.0978

AC:

1037

AN:

10608

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8364

AN:

68014

Other (OTH)

AF:

0.0989

AC:

209

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

613

1226

1840

2453

3066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0744

Hom.:

242

Bravo

AF:

0.0847

Asia WGS

AF:

0.0480

AC:

168

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs6706649

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