2-177263111-T-C

Position:

• chr2-177263111-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+1421A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,210 control chromosomes in the GnomAD database, including 7,617 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 0.30 (7617 hom., cov: 34)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFE2L2	NM_006164.5	c.45+1421A>G		intron_variant		ENST00000397062.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFE2L2	ENST00000397062.8	c.45+1421A>G		intron_variant		1	NM_006164.5	A1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45752 AN: 152092 Hom.: 7598 Cov.: 34

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.301 AC: 45785 AN: 152210 Hom.: 7617 Cov.: 34 AF XY: 0.311 AC XY: 23108 AN XY: 74408

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.292

Alfa AF: 0.196 Hom.: 421

Bravo AF: 0.293

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2886161; hg19: chr2-178127839;