rs2001350

Variant names:

• chr2-177235697-C-T
• rs2001350
• NM_006164.5:c.46-1426G>A

Variant summary

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

The NM_006164.5(NFE2L2):​c.46-1426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,062 control chromosomes in the GnomAD database, including 60,147 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 0.89 (60147 hom., cov: 29)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• Publications: 21 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L2	NM_006164.5	c.46-1426G>A		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.46-1426G>A		intron_variant	Intron 1 of 4	1	NM_006164.5	ENSP00000380252.3

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135043 AN: 151944 Hom.: 60094 Cov.: 29

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.898

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

GnomAD4 genome AF: 0.889 AC: 135154 AN: 152062 Hom.: 60147 Cov.: 29 AF XY: 0.886 AC XY: 65855 AN XY: 74308

African (AFR) AF: 0.889 AC: 36885 AN: 41468

American (AMR) AF: 0.905 AC: 13826 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3071 AN: 3466

East Asian (EAS) AF: 0.745 AC: 3830 AN: 5142

South Asian (SAS) AF: 0.889 AC: 4281 AN: 4818

European-Finnish (FIN) AF: 0.853 AC: 9014 AN: 10568

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.901 AC: 61282 AN: 68006

Other (OTH) AF: 0.900 AC: 1900 AN: 2112

Alfa AF: 0.898 Hom.: 192830

Bravo AF: 0.893

Asia WGS AF: 0.839 AC: 2921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.88
DANN	Benign	0.18
PhyloP100		-0.63
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: rs2001350; hg19: chr2-178100425;