rs13005431

Positions:

• chr2-177256384-T-C

Variant summary

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

The NM_006164.5(NFE2L2):​c.45+8148A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,772 control chromosomes in the GnomAD database, including 8,323 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 0.32 (8323 hom., cov: 29)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFE2L2	NM_006164.5	c.45+8148A>G		intron_variant		ENST00000397062.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFE2L2	ENST00000397062.8	c.45+8148A>G		intron_variant		1	NM_006164.5	A1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49288 AN: 151652 Hom.: 8313 Cov.: 29

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.317

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.325 AC: 49325 AN: 151772 Hom.: 8323 Cov.: 29 AF XY: 0.315 AC XY: 23358 AN XY: 74168

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.360

Alfa AF: 0.337 Hom.: 1084

Bravo AF: 0.327

Asia WGS AF: 0.156 AC: 547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.46
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: rs13005431; hg19: chr2-178121112;