rs2706112

chr2-177225133-G-Achr2-177225133-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000699342.1(NFE2L2):c.715-2501C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,114 control chromosomes in the GnomAD database, including 38,826 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 0.70 (38826 hom., cov: 34)
• Consequence: NFE2L2 ENST00000699342.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329

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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFE2L2	ENST00000699220.1	c.595-2501C>T		intron_variant
NFE2L2	ENST00000699296.1	c.595-2501C>T		intron_variant
NFE2L2	ENST00000699297.1	c.547-2501C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105745 AN: 151998 Hom.: 38816 Cov.: 34

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.695 AC: 105772 AN: 152114 Hom.: 38826 Cov.: 34 AF XY: 0.697 AC XY: 51833 AN XY: 74374

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.734

Alfa AF: 0.745 Hom.: 5402

Bravo AF: 0.687

Asia WGS AF: 0.758 AC: 2635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.71
Dann	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2706112; hg19: chr2-178089861;