rs2364722

Variant names:

• chr2-177260059-A-G
• rs2364722
• NM_006164.5:c.45+4473T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006164.5(NFE2L2):​c.45+4473T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,158 control chromosomes in the GnomAD database, including 7,603 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 0.30 (7603 hom., cov: 33)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• Publications: 19 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L2	NM_006164.5	c.45+4473T>C		intron_variant	Intron 1 of 4	ENST00000397062.8	NP_006155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFE2L2	ENST00000397062.8	c.45+4473T>C		intron_variant	Intron 1 of 4	1	NM_006164.5	ENSP00000380252.3

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45761 AN: 152040 Hom.: 7584 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.287

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.301 AC: 45794 AN: 152158 Hom.: 7603 Cov.: 33 AF XY: 0.311 AC XY: 23108 AN XY: 74384

African (AFR) AF: 0.181 AC: 7507 AN: 41540

American (AMR) AF: 0.401 AC: 6133 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3472

East Asian (EAS) AF: 0.522 AC: 2702 AN: 5176

South Asian (SAS) AF: 0.482 AC: 2326 AN: 4822

European-Finnish (FIN) AF: 0.357 AC: 3772 AN: 10554

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21580 AN: 67976

Other (OTH) AF: 0.292 AC: 618 AN: 2116

Alfa AF: 0.312 Hom.: 24717

Bravo AF: 0.293

Asia WGS AF: 0.526 AC: 1831 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.4
DANN	Benign	0.68
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2364722; hg19: chr2-178124787;