rs2001297

Variant names:

• chr2-177253822-C-A
• rs2001297
• NM_006164.5:c.45+10710G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-177253822-C-A
• chr2-177253822-C-T

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+10710G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,224 control chromosomes in the GnomAD database, including 53,352 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 0.83 (53352 hom., cov: 33)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 2 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: Illumina, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.877 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	NM_006164.5	MANE Select	c.45+10710G>T		intron	N/A	NP_006155.2
	NFE2L2	NM_001145412.3		c.-4+9581G>T		intron	N/A	NP_001138884.1	Q16236-2
	NFE2L2	NM_001313900.1		c.-4+9707G>T		intron	N/A	NP_001300829.1	Q16236-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	ENST00000397062.8	TSL:1 MANE Select	c.45+10710G>T		intron	N/A	ENSP00000380252.3	Q16236-1
	NFE2L2	ENST00000397063.9	TSL:1	c.-4+9581G>T		intron	N/A	ENSP00000380253.4	Q16236-2
	NFE2L2	ENST00000421929.6	TSL:1	c.-4+9707G>T		intron	N/A	ENSP00000412191.2	Q16236-2

Frequencies

GnomAD3 genomes AF: 0.835 AC: 127010 AN: 152106 Hom.: 53312 Cov.: 33

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.855

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

GnomAD4 genome AF: 0.835 AC: 127095 AN: 152224 Hom.: 53352 Cov.: 33 AF XY: 0.833 AC XY: 61995 AN XY: 74428

African (AFR) AF: 0.755 AC: 31341 AN: 41500

American (AMR) AF: 0.837 AC: 12799 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3052 AN: 3472

East Asian (EAS) AF: 0.753 AC: 3905 AN: 5186

South Asian (SAS) AF: 0.847 AC: 4089 AN: 4828

European-Finnish (FIN) AF: 0.849 AC: 8990 AN: 10594

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 60055 AN: 68026

Other (OTH) AF: 0.856 AC: 1809 AN: 2114

Alfa AF: 0.853 Hom.: 6877

Bravo AF: 0.828

Asia WGS AF: 0.823 AC: 2865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.61
PhyloP100		-0.22
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: rs2001297; hg19: chr2-178118550;