rs2886161

Variant names:

• chr2-177263111-T-C
• rs2886161
• NM_006164.5:c.45+1421A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-177263111-T-C
• chr2-177263111-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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=-0.81).
• 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 rank	MANE	Protein	UniProt
NFE2L2	NM_006164.5	c.45+1421A>G		intron_variant	Intron 1 of 4	ENST00000397062.8	NP_006155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFE2L2	ENST00000397062.8	c.45+1421A>G		intron_variant	Intron 1 of 4	1	NM_006164.5	ENSP00000380252.3

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

African (AFR) AF: 0.180 AC: 7475 AN: 41550

American (AMR) AF: 0.401 AC: 6131 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3472

East Asian (EAS) AF: 0.523 AC: 2713 AN: 5190

South Asian (SAS) AF: 0.494 AC: 2382 AN: 4826

European-Finnish (FIN) AF: 0.356 AC: 3770 AN: 10576

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.317 AC: 21541 AN: 67986

Other (OTH) AF: 0.292 AC: 618 AN: 2114

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
PhyloP100		-0.35
PromoterAI		0.0022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2886161; hg19: chr2-178127839;