rs13035806

chr2-177227094-G-A

Variant summary

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

The ENST00000699342.1(NFE2L2):c.715-4462C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,132 control chromosomes in the GnomAD database, including 2,190 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 0.15 (2190 hom., cov: 33)
• Consequence: NFE2L2 ENST00000699342.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.517

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 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.595-4462C>T		intron_variant
NFE2L2	ENST00000699296.1	c.595-4462C>T		intron_variant
NFE2L2	ENST00000699297.1	c.547-4462C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22657 AN: 152016 Hom.: 2185 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0889

Gnomad ASJ AF: 0.0904

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.149 AC: 22684 AN: 152132 Hom.: 2190 Cov.: 33 AF XY: 0.146 AC XY: 10864 AN XY: 74394

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.0887

Gnomad4 ASJ AF: 0.0904

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0377

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.130

Alfa AF: 0.116 Hom.: 1103

Bravo AF: 0.154

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.1
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13035806; hg19: chr2-178091822; COSMIC: COSV67962673;