chr2-177248756-A-G

Variant names:

• chr2-177248756-A-G
• rs1962142
• NM_006164.5:c.46-14485T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006164.5(NFE2L2):​c.46-14485T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,130 control chromosomes in the GnomAD database, including 62,258 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 0.90 (62258 hom., cov: 31)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• Publications: 23 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L2	NM_006164.5	c.46-14485T>C		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.46-14485T>C		intron_variant	Intron 1 of 4	1	NM_006164.5	ENSP00000380252.3

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137395 AN: 152012 Hom.: 62205 Cov.: 31

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.913

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

GnomAD4 genome AF: 0.904 AC: 137505 AN: 152130 Hom.: 62258 Cov.: 31 AF XY: 0.902 AC XY: 67084 AN XY: 74360

African (AFR) AF: 0.945 AC: 39217 AN: 41508

American (AMR) AF: 0.869 AC: 13295 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 3100 AN: 3470

East Asian (EAS) AF: 0.792 AC: 4094 AN: 5166

South Asian (SAS) AF: 0.908 AC: 4378 AN: 4820

European-Finnish (FIN) AF: 0.875 AC: 9233 AN: 10558

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61193 AN: 68002

Other (OTH) AF: 0.914 AC: 1928 AN: 2110

Alfa AF: 0.900 Hom.: 101420

Bravo AF: 0.903

Asia WGS AF: 0.861 AC: 2996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.41
PhyloP100		-2.5
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: rs1962142; hg19: chr2-178113484;