rs6726395

Positions:

• chr2-177238501-A-G

Variant summary

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

The NM_006164.5(NFE2L2):​c.46-4230T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,066 control chromosomes in the GnomAD database, including 21,391 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 0.52 (21391 hom., cov: 33)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFE2L2	NM_006164.5	c.46-4230T>C		intron_variant		ENST00000397062.8	NP_006155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFE2L2	ENST00000397062.8	c.46-4230T>C		intron_variant		1	NM_006164.5	ENSP00000380252	A1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79616 AN: 151948 Hom.: 21374 Cov.: 33

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.524 AC: 79661 AN: 152066 Hom.: 21391 Cov.: 33 AF XY: 0.531 AC XY: 39456 AN XY: 74330

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.522

Alfa AF: 0.551 Hom.: 47827

Bravo AF: 0.518

Asia WGS AF: 0.665 AC: 2314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6726395; hg19: chr2-178103229;