rs7557529

Variant names:

• chr2-177270369-C-T
• rs7557529
• ENST00000699346.1:c.183+26178G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000699346.1(NFE2L2):​c.183+26178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,952 control chromosomes in the GnomAD database, including 23,218 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 0.55 (23218 hom., cov: 32)
• Consequence: NFE2L2 ENST00000699346.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 14 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFE2L2	ENST00000699346.1	c.183+26178G>A		intron_variant	Intron 7 of 10			ENSP00000514321.1
NFE2L2	ENST00000586532.6	c.43-36098G>A		intron_variant	Intron 3 of 6	5		ENSP00000464920.2
NFE2L2	ENST00000699265.1	c.43-36098G>A		intron_variant	Intron 5 of 8			ENSP00000514246.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83794 AN: 151832 Hom.: 23186 Cov.: 32

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.552 AC: 83869 AN: 151952 Hom.: 23218 Cov.: 32 AF XY: 0.558 AC XY: 41439 AN XY: 74266

African (AFR) AF: 0.584 AC: 24202 AN: 41440

American (AMR) AF: 0.567 AC: 8663 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1753 AN: 3468

East Asian (EAS) AF: 0.609 AC: 3144 AN: 5164

South Asian (SAS) AF: 0.689 AC: 3321 AN: 4820

European-Finnish (FIN) AF: 0.562 AC: 5912 AN: 10528

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34999 AN: 67950

Other (OTH) AF: 0.512 AC: 1079 AN: 2108

Alfa AF: 0.537 Hom.: 8433

Bravo AF: 0.550

Asia WGS AF: 0.658 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.45
PhyloP100		-0.079
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7557529; hg19: chr2-178135097;