rs72946143

Variant names:

• chr2-177258401-T-C
• rs72946143
• NM_006164.5:c.45+6131A>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+6131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.04 in 152,248 control chromosomes in the GnomAD database, including 176 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 0.040 (176 hom., cov: 32)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L2	NM_006164.5	c.45+6131A>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+6131A>G		intron_variant	Intron 1 of 4	1	NM_006164.5	ENSP00000380252.3

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 6082 AN: 152130 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.00987

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0320

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0827

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0400 AC: 6084 AN: 152248 Hom.: 176 Cov.: 32 AF XY: 0.0392 AC XY: 2921 AN XY: 74422

African (AFR) AF: 0.00984 AC: 409 AN: 41546

American (AMR) AF: 0.0320 AC: 489 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4828

European-Finnish (FIN) AF: 0.0827 AC: 875 AN: 10586

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0596 AC: 4056 AN: 68020

Other (OTH) AF: 0.0388 AC: 82 AN: 2116

Alfa AF: 0.0479 Hom.: 43

Bravo AF: 0.0354

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.64
PhyloP100		0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs72946143; hg19: chr2-178123129;