2-177227434-T-C

Variant names:

• chr2-177227434-T-C
• rs2706110
• ENST00000458603.2:c.*472A>G

Variant summary

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

The ENST00000458603.2(NFE2L2):​c.*472A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,102 control chromosomes in the GnomAD database, including 38,464 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 0.69 (38464 hom., cov: 32)
• Consequence: NFE2L2 ENST00000458603.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.654
• Publications: 29 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.818 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	ENST00000458603.2	c.*472A>G		3_prime_UTR_variant	Exon 5 of 5	3		ENSP00000416308.2
NFE2L2	ENST00000699342.1	c.714+4455A>G		intron_variant	Intron 5 of 6			ENSP00000514317.1
NFE2L2	ENST00000699404.1	c.711+4455A>G		intron_variant	Intron 9 of 10			ENSP00000514365.1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104601 AN: 151984 Hom.: 38453 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.688 AC: 104629 AN: 152102 Hom.: 38464 Cov.: 32 AF XY: 0.690 AC XY: 51297 AN XY: 74372

African (AFR) AF: 0.398 AC: 16519 AN: 41454

American (AMR) AF: 0.794 AC: 12149 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2864 AN: 3472

East Asian (EAS) AF: 0.752 AC: 3881 AN: 5164

South Asian (SAS) AF: 0.840 AC: 4054 AN: 4828

European-Finnish (FIN) AF: 0.751 AC: 7956 AN: 10592

Middle Eastern (MID) AF: 0.750 AC: 219 AN: 292

European-Non Finnish (NFE) AF: 0.805 AC: 54736 AN: 67986

Other (OTH) AF: 0.726 AC: 1532 AN: 2110

Alfa AF: 0.771 Hom.: 58220

Bravo AF: 0.678

Asia WGS AF: 0.760 AC: 2643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.71
PhyloP100		0.65

Splicing

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

Other links and lift over

dbSNP: rs2706110; hg19: chr2-178092162;