rs6706649

Positions:

• chr2-177265343-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000464747.5(NFE2L2):​c.-3-31072G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 203,304 control chromosomes in the GnomAD database, including 1,065 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 0.088 (744 hom., cov: 34)
  • Exomes 𝑓: 0.10 (321 hom.)
• Consequence: NFE2L2 ENST00000464747.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.707

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.177265343C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFE2L2	ENST00000699346.1	c.184-31072G>A		intron_variant				ENSP00000514321.1
NFE2L2	ENST00000586532.6	c.43-31072G>A		intron_variant		5		ENSP00000464920.2
NFE2L2	ENST00000699265.1	c.43-31072G>A		intron_variant				ENSP00000514246.1

Frequencies

GnomAD3 genomes AF: 0.0877 AC: 13345 AN: 152174 Hom.: 744 Cov.: 34

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0793

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0605

Gnomad SAS AF: 0.0981

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0999

GnomAD4 exome AF: 0.104 AC: 5308 AN: 51012 Hom.: 321 Cov.: 0 AF XY: 0.107 AC XY: 2551 AN XY: 23904

Gnomad4 AFR exome AF: 0.0185

Gnomad4 AMR exome AF: 0.0704

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.0478

Gnomad4 SAS exome AF: 0.0750

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.0876 AC: 13347 AN: 152292 Hom.: 744 Cov.: 34 AF XY: 0.0863 AC XY: 6422 AN XY: 74452

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.0793

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.0604

Gnomad4 SAS AF: 0.0983

Gnomad4 FIN AF: 0.0978

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.0989

Alfa AF: 0.0882 Hom.: 118

Bravo AF: 0.0847

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6706649; hg19: chr2-178130071;