rs2364720

Variant names:

• chr2-177240416-A-G
• rs2364720
• NM_006164.5:c.46-6145T>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.46-6145T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,188 control chromosomes in the GnomAD database, including 56,517 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 0.86 (56517 hom., cov: 32)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006164.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	NM_006164.5	MANE Select	c.46-6145T>C		intron	N/A	NP_006155.2
	NFE2L2	NM_001145412.3		c.-3-6145T>C		intron	N/A	NP_001138884.1
	NFE2L2	NM_001313900.1		c.-3-6145T>C		intron	N/A	NP_001300829.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	ENST00000397062.8	TSL:1 MANE Select	c.46-6145T>C		intron	N/A	ENSP00000380252.3
	NFE2L2	ENST00000397063.9	TSL:1	c.-3-6145T>C		intron	N/A	ENSP00000380253.4
	NFE2L2	ENST00000421929.6	TSL:1	c.-3-6145T>C		intron	N/A	ENSP00000412191.2

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130888 AN: 152070 Hom.: 56469 Cov.: 32

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.879

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

GnomAD4 genome AF: 0.861 AC: 130991 AN: 152188 Hom.: 56517 Cov.: 32 AF XY: 0.858 AC XY: 63843 AN XY: 74394

African (AFR) AF: 0.813 AC: 33744 AN: 41510

American (AMR) AF: 0.852 AC: 13029 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 3101 AN: 3472

East Asian (EAS) AF: 0.742 AC: 3831 AN: 5162

South Asian (SAS) AF: 0.890 AC: 4294 AN: 4826

European-Finnish (FIN) AF: 0.853 AC: 9027 AN: 10586

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.897 AC: 61042 AN: 68028

Other (OTH) AF: 0.880 AC: 1861 AN: 2114

Alfa AF: 0.872 Hom.: 7500

Bravo AF: 0.856

Asia WGS AF: 0.831 AC: 2892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.33
PhyloP100		-0.69
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: rs2364720; hg19: chr2-178105144;