rs2001297

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFE2L2	NM_006164.5	c.45+10710G>T		intron_variant		ENST00000397062.8	NP_006155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFE2L2	ENST00000397062.8	c.45+10710G>T		intron_variant		1	NM_006164.5	ENSP00000380252	A1

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

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.879

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.849

Gnomad4 NFE AF: 0.883

Gnomad4 OTH AF: 0.856

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs2001297; hg19: chr2-178118550;