2-177253424-C-T

Position:

• chr2-177253424-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.45+11108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,194 control chromosomes in the GnomAD database, including 2,861 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 0.17 (2861 hom., cov: 33)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFE2L2	NM_006164.5	c.45+11108G>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.45+11108G>A		intron_variant		1	NM_006164.5	ENSP00000380252.3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26195 AN: 152076 Hom.: 2861 Cov.: 33

Gnomad AFR AF: 0.0477

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0813

Gnomad SAS AF: 0.0931

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.172 AC: 26192 AN: 152194 Hom.: 2861 Cov.: 33 AF XY: 0.166 AC XY: 12321 AN XY: 74412

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.0811

Gnomad4 SAS AF: 0.0938

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.215

Alfa AF: 0.230 Hom.: 5918

Bravo AF: 0.170

Asia WGS AF: 0.0790 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.64

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: rs1806649; hg19: chr2-178118152;