rs2364720

Positions:

• chr2-177240416-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.46-6145T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,188 control chromosomes in the GnomAD database, including 56,517 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 0.86 (56517 hom., cov: 32)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFE2L2	NM_006164.5	c.46-6145T>C		intron_variant		ENST00000397062.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFE2L2	ENST00000397062.8	c.46-6145T>C		intron_variant		1	NM_006164.5	A1

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130888 AN: 152070 Hom.: 56469 Cov.: 32

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.879

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

GnomAD4 genome AF: 0.861 AC: 130991 AN: 152188 Hom.: 56517 Cov.: 32 AF XY: 0.858 AC XY: 63843 AN XY: 74394

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.893

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.897

Gnomad4 OTH AF: 0.880

Alfa AF: 0.875 Hom.: 7242

Bravo AF: 0.856

Asia WGS AF: 0.831 AC: 2892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.33

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: rs2364720; hg19: chr2-178105144;