ENST00000699346.1:c.184-31038A>G

Variant names:

• chr2-177265309-T-C
• rs6721961
• ENST00000699346.1:c.184-31038A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000699346.1(NFE2L2):​c.184-31038A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NFE2L2 ENST00000699346.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• Publications: 169 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: Illumina, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000222043 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000699346.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	ENST00000699346.1		c.184-31038A>G		intron	N/A	ENSP00000514321.1	A0A8V8TNM0
	NFE2L2	ENST00000586532.6	TSL:5	c.43-31038A>G		intron	N/A	ENSP00000464920.2	K7EIW5
	NFE2L2	ENST00000699265.1		c.43-31038A>G		intron	N/A	ENSP00000514246.1	K7EIW5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 61768 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 28882

African (AFR) AF: 0.00 AC: 0 AN: 2666

American (AMR) AF: 0.00 AC: 0 AN: 1788

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3830

East Asian (EAS) AF: 0.00 AC: 0 AN: 9406

South Asian (SAS) AF: 0.00 AC: 0 AN: 566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 368

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 37900

Other (OTH) AF: 0.00 AC: 0 AN: 5070

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.6
DANN	Benign	0.76
PhyloP100		0.22
PromoterAI		0.072	Neutral

Splicing

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

Other links and lift over

dbSNP: rs6721961; hg19: chr2-178130037;