chr2-177232938-C-T

Variant names:

• chr2-177232938-C-T
• rs10183914
• ENST00000423513.6:n.804G>A

Variant summary

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

The ENST00000423513.6(NFE2L2):​n.804G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 480,368 control chromosomes in the GnomAD database, including 24,213 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 (7914 hom., cov: 32)
  • Exomes 𝑓: 0.30 (16299 hom.)
• Consequence: NFE2L2 ENST00000423513.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 25 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000423513.6. 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.402+312G>A		intron	N/A	NP_006155.2
	NFE2L2	NM_001145412.3		c.354+312G>A		intron	N/A	NP_001138884.1
	NFE2L2	NM_001313900.1		c.354+312G>A		intron	N/A	NP_001300829.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	ENST00000423513.6	TSL:1	n.804G>A		non_coding_transcript_exon	Exon 3 of 3
	NFE2L2	ENST00000477534.2	TSL:1	n.1469G>A		non_coding_transcript_exon	Exon 2 of 3
	NFE2L2	ENST00000397062.8	TSL:1 MANE Select	c.402+312G>A		intron	N/A	ENSP00000380252.3

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48024 AN: 151880 Hom.: 7912 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.0662

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.296 AC: 97169 AN: 328370 Hom.: 16299 Cov.: 2 AF XY: 0.291 AC XY: 49566 AN XY: 170528

African (AFR) AF: 0.326 AC: 2678 AN: 8214

American (AMR) AF: 0.226 AC: 2437 AN: 10772

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 3922 AN: 11000

East Asian (EAS) AF: 0.0413 AC: 1028 AN: 24900

South Asian (SAS) AF: 0.126 AC: 2792 AN: 22218

European-Finnish (FIN) AF: 0.294 AC: 6656 AN: 22668

Middle Eastern (MID) AF: 0.289 AC: 453 AN: 1570

European-Non Finnish (NFE) AF: 0.343 AC: 70867 AN: 206804

Other (OTH) AF: 0.313 AC: 6336 AN: 20224

GnomAD4 genome AF: 0.316 AC: 48049 AN: 151998 Hom.: 7914 Cov.: 32 AF XY: 0.307 AC XY: 22808 AN XY: 74308

African (AFR) AF: 0.331 AC: 13714 AN: 41448

American (AMR) AF: 0.267 AC: 4077 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1225 AN: 3470

East Asian (EAS) AF: 0.0660 AC: 341 AN: 5168

South Asian (SAS) AF: 0.128 AC: 618 AN: 4830

European-Finnish (FIN) AF: 0.281 AC: 2963 AN: 10554

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24126 AN: 67940

Other (OTH) AF: 0.338 AC: 711 AN: 2106

Alfa AF: 0.321 Hom.: 1611

Bravo AF: 0.320

Asia WGS AF: 0.113 AC: 395 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.56
PhyloP100		-0.032
PromoterAI		0.0066	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10183914; hg19: chr2-178097666;