rs35652124

Variant names:

• chr2-177265345-T-A
• rs35652124
• ENST00000699346.1:c.184-31074A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-177265345-T-A
• chr2-177265345-T-C
• chr2-177265345-T-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.184-31074A>T 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NFE2L2 ENST00000699346.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 90 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

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=-0.57).

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.184-31074A>T		intron_variant	Intron 7 of 10			ENSP00000514321.1
NFE2L2	ENST00000586532.6	c.43-31074A>T		intron_variant	Intron 3 of 6	5		ENSP00000464920.2
NFE2L2	ENST00000699265.1	c.43-31074A>T		intron_variant	Intron 5 of 8			ENSP00000514246.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 47758 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 22310

African (AFR) AF: 0.00 AC: 0 AN: 1976

American (AMR) AF: 0.00 AC: 0 AN: 1272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2942

East Asian (EAS) AF: 0.00 AC: 0 AN: 7968

South Asian (SAS) AF: 0.00 AC: 0 AN: 436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 28844

Other (OTH) AF: 0.00 AC: 0 AN: 3910

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.74
PhyloP100		2.0

Splicing

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

Other links and lift over

dbSNP: rs35652124; hg19: chr2-178130073;