rs13005431

Variant names:

• chr2-177256384-T-C
• rs13005431
• NM_006164.5:c.45+8148A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000397062.8(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 ENST00000397062.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 7 publications found

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]

NFE2L2 Gene-Disease associations (from GenCC):

• immunodeficiency, developmental delay, and hypohomocysteinemia

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397062.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	NM_006164.5	MANE Select	c.45+8148A>G		intron	N/A	NP_006155.2
	NFE2L2	NM_001145412.3		c.-4+7019A>G		intron	N/A	NP_001138884.1
	NFE2L2	NM_001313900.1		c.-4+7145A>G		intron	N/A	NP_001300829.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	ENST00000397062.8	TSL:1 MANE Select	c.45+8148A>G		intron	N/A	ENSP00000380252.3
	NFE2L2	ENST00000397063.9	TSL:1	c.-4+7019A>G		intron	N/A	ENSP00000380253.4
	NFE2L2	ENST00000421929.6	TSL:1	c.-4+7145A>G		intron	N/A	ENSP00000412191.2

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

African (AFR) AF: 0.319 AC: 13178 AN: 41350

American (AMR) AF: 0.280 AC: 4273 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1289 AN: 3468

East Asian (EAS) AF: 0.121 AC: 624 AN: 5160

South Asian (SAS) AF: 0.161 AC: 777 AN: 4820

European-Finnish (FIN) AF: 0.285 AC: 2997 AN: 10510

Middle Eastern (MID) AF: 0.321 AC: 93 AN: 290

European-Non Finnish (NFE) AF: 0.371 AC: 25160 AN: 67904

Other (OTH) AF: 0.360 AC: 756 AN: 2098

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.46
DANN	Benign	0.33
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13005431; hg19: chr2-178121112;