rs4243387

Variant names:

• chr2-177253037-C-T
• rs4243387
• NM_006164.5:c.45+11495G>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.45+11495G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,138 control chromosomes in the GnomAD database, including 46,028 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 0.76 (46028 hom., cov: 32)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918
• Publications: 14 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L2	NM_006164.5	c.45+11495G>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.45+11495G>A		intron_variant	Intron 1 of 4	1	NM_006164.5	ENSP00000380252.3

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115684 AN: 152020 Hom.: 46014 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.761 AC: 115714 AN: 152138 Hom.: 46028 Cov.: 32 AF XY: 0.761 AC XY: 56628 AN XY: 74376

African (AFR) AF: 0.507 AC: 21009 AN: 41462

American (AMR) AF: 0.809 AC: 12370 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 3021 AN: 3470

East Asian (EAS) AF: 0.718 AC: 3726 AN: 5186

South Asian (SAS) AF: 0.819 AC: 3951 AN: 4822

European-Finnish (FIN) AF: 0.848 AC: 8979 AN: 10588

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.881 AC: 59923 AN: 67998

Other (OTH) AF: 0.797 AC: 1687 AN: 2116

Alfa AF: 0.809 Hom.: 6337

Bravo AF: 0.744

Asia WGS AF: 0.759 AC: 2642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.57
DANN	Benign	0.51
PhyloP100		-0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4243387; hg19: chr2-178117765;