rs13035806

Variant names:

• chr2-177227094-G-A
• rs13035806
• ENST00000699342.1:c.715-4462C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000699342.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	ENST00000699342.1		c.715-4462C>T		intron	N/A	ENSP00000514317.1
	NFE2L2	ENST00000699404.1		c.712-4462C>T		intron	N/A	ENSP00000514365.1
	NFE2L2	ENST00000699405.1		c.715-4462C>T		intron	N/A	ENSP00000514366.1

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

African (AFR) AF: 0.281 AC: 11670 AN: 41498

American (AMR) AF: 0.0887 AC: 1355 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0904 AC: 314 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.0377 AC: 182 AN: 4826

European-Finnish (FIN) AF: 0.116 AC: 1231 AN: 10604

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7546 AN: 67972

Other (OTH) AF: 0.130 AC: 274 AN: 2110

Alfa AF: 0.122 Hom.: 1680

Bravo AF: 0.154

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.74
PhyloP100		-0.52

Splicing

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

Other links and lift over

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