rs1962142

Positions:

• chr2-177248756-A-G
• chr2-177248756-A-T

Variant summary

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

The NM_006164.5(NFE2L2):​c.46-14485T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,130 control chromosomes in the GnomAD database, including 62,258 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 0.90 (62258 hom., cov: 31)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFE2L2	NM_006164.5	c.46-14485T>C		intron_variant		ENST00000397062.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFE2L2	ENST00000397062.8	c.46-14485T>C		intron_variant		1	NM_006164.5	A1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137395 AN: 152012 Hom.: 62205 Cov.: 31

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.913

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

GnomAD4 genome AF: 0.904 AC: 137505 AN: 152130 Hom.: 62258 Cov.: 31 AF XY: 0.902 AC XY: 67084 AN XY: 74360

Gnomad4 AFR AF: 0.945

Gnomad4 AMR AF: 0.869

Gnomad4 ASJ AF: 0.893

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.908

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.900

Gnomad4 OTH AF: 0.914

Alfa AF: 0.899 Hom.: 79081

Bravo AF: 0.903

Asia WGS AF: 0.861 AC: 2996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.41

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: rs1962142; hg19: chr2-178113484;