rs10183914

Positions:

• chr2-177232938-C-T

Variant summary

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

The NM_006164.5(NFE2L2):​c.402+312G>A variant causes a intron 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 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFE2L2	NM_006164.5	c.402+312G>A		intron_variant		ENST00000397062.8	NP_006155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFE2L2	ENST00000397062.8	c.402+312G>A		intron_variant		1	NM_006164.5	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

Gnomad4 AFR exome AF: 0.326

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.0413

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.294

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.313

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

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.0660

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.338

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs10183914; hg19: chr2-178097666;